57 results on '"CHENG-CAO SUN"'
Search Results
2. FOXC1-mediated LINC00301 facilitates tumor progression and triggers an immune-suppressing microenvironment in non-small cell lung cancer by regulating the HIF1α pathway
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Cheng-Cao Sun, Wei Zhu, Shu-Jun Li, Wei Hu, Jian Zhang, Yue Zhuo, Han Zhang, Juan Wang, Yu Zhang, Shao-Xin Huang, Qi-Qiang He, and De-Jia Li
- Subjects
LINC00301 ,ELL protein-associated factor 2 (EAF2) ,Non-small cell lung cancer (NSCLC) ,Enhancer of zeste homolog 2 (EZH2) ,Regulatory T cells (Treg) ,Hypoxia-inducible factor 1 α (HIF1α) ,Medicine ,Genetics ,QH426-470 - Abstract
Abstract Background Long non-coding RNAs (lncRNAs) are extensively intricate in the tumorigenesis and metastasis of various cancer types. Nevertheless, the detailed molecular mechanisms of lncRNA in non-small cell lung cancer (NSCLC) still remain mainly undetermined. Methods qPCR was performed to verify LINC00301 expression in NSCLC clinical specimens or cell lines. Fluorescence in situ hybridization (FISH) was conducted to identify the localization of LINC00301 in NSCLC cells. Chromatin immunoprecipitation (ChIP) was subjected to validate the binding activity between FOXC1 and LINC00301 promoters. RNA immunoprecipitation (RIP) was performed to explore the binding activity between LINC00301 and EZH2. RNA pull-down followed by dot-blot, protein domain mapping, and RNA electrophoresis mobility shift assay (EMSA) were conducted to identify the detailed binding regions between LINC00301 and EZH2. Alpha assay was conducted to quantitatively assess the interaction between LINC00301 and EZH2. Results LINC00301 is highly expressed in NSCLC and closely corelated to its prognosis by analyzing the relationship between differentially expressed lncRNAs and prognosis in NSCLC samples. in vitro and in vivo experiments revealed that LINC00301 facilitates cell proliferation, releases NSCLC cell cycle arrest, promotes cell migration and invasion, and suppresses cell apoptosis in NSCLC. In addition, LINC00301 increases regulatory T cell (Treg) while decreases CD8+ T cell population in LA-4/SLN-205-derived tumors through targeting TGF-β. The transcription factor FOXC1 mediates LINC00301 expression in NSCLC. Bioinformatics prediction and in vitro experiments indicated that LINC00301 (83–123 nucleotide [nt]) can directly bind to the enhancer of zeste homolog 2 (EZH2) (612–727 amino acid [aa]) to promote H3K27me3 at the ELL protein-associated factor 2 (EAF2) promoter. EAF2 directly binds and stabilizes von Hippel–Lindau protein (pVHL), so downregulated EAF2 augments hypoxia-inducible factor 1 α (HIF1α) expression by regulating pVHL in NSCLC cells. Moreover, we also found that LINC00301 could function as a competing endogenous RNA (ceRNA) against miR-1276 to expedite HIF1α expression in the cytoplasm of NSCLC cells. Conclusions In summary, our present research revealed the oncogenic roles of LINC00301 in clinical specimens as well as cellular and animal experiments, illustrating the potential roles and mechanisms of the FOXC1/LINC00301/EZH2/EAF2/pVHL/HIF1α and FOXC1/LINC00301/miR-1276/HIF1α pathways, which provides novel insights and potential theraputic targets to NSCLC.
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- 2020
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3. Comprehensive landscape of extracellular vesicle-derived RNAs in cancer initiation, progression, metastasis and cancer immunology
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Wei Hu, Cong Liu, Zhuo-Yue Bi, Qun Zhou, Han Zhang, Lin-Lin Li, Jian Zhang, Wei Zhu, Yang-Yi-Yan Song, Feng Zhang, Hui-Min Yang, Yong-Yi Bi, Qi-Qiang He, Gong-Jun Tan, Cheng-Cao Sun, and De-Jia Li
- Subjects
Extracellular vesicle ,Exosome ,Microvesicle ,Micro RNA ,Long non-coding RNA ,Circular RNA ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Extracellular vesicles (EVs), a class of heterogeneous membrane vesicles, are generally divided into exosomes and microvesicles on basis of their origination from the endosomal membrane or the plasma membrane, respectively. EV-mediated bidirectional communication among various cell types supports cancer cell growth and metastasis. EVs derived from different cell types and status have been shown to have distinct RNA profiles, comprising messenger RNAs and non-coding RNAs (ncRNAs). Recently, ncRNAs have attracted great interests in the field of EV-RNA research, and growing numbers of ncRNAs ranging from microRNAs to long ncRNAs have been investigated to reveal their specific functions and underlying mechanisms in the tumor microenvironment and premetastatic niches. Emerging evidence has indicated that EV-RNAs are essential functional cargoes in modulating hallmarks of cancers and in reciprocal crosstalk within tumor cells and between tumor and stromal cells over short and long distance, thereby regulating the initiation, development and progression of cancers. In this review, we discuss current findings regarding EV biogenesis, release and interaction with target cells as well as EV-RNA sorting, and highlight biological roles and molecular mechanisms of EV-ncRNAs in cancer biology.
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- 2020
- Full Text
- View/download PDF
4. Correction to: FOXC1-mediated LINC00301 facilitates tumor progression and triggers an immune-suppressing microenvironment in non-small cell lung cancer by regulating the HIF1α pathway
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Cheng-Cao Sun, Wei Zhu, Shu-Jun Li, Wei Hu, Jian Zhang, Yue Zhuo, Han Zhang, Juan Wang, Yu Zhang, Shao-Xin Huang, Qi-Qiang He, and De-Jia Li
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Medicine ,Genetics ,QH426-470 - Abstract
An amendment to this paper has been published and can be accessed via the original article.
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- 2021
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5. Expression and Prognosis Analyses of Runt-Related Transcription Factor Family in Human Leukemia
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Cheng-Cao Sun, Shu-Jun Li, Zhen-Long Chen, Guang Li, Qian Zhang, and De-Jia Li
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Despite advances in early diagnosis and treatment, cancer remains the major reason for mortality worldwide. The Runt-related transcription factor (RUNX) family has been reported to participate in diverse human diseases. However, little is known about their expression and prognostic values in human leukemia. Herein, we conducted a detailed cancer versus normal analysis. The mRNA expression levels of the RUNX family in various kinds of cancers, including leukemia, were analyzed via the ONCOMINE and GEPIA (Gene Expression Profiling Interactive Analysis) databases. We observed that the mRNA expression levels of RUNX1, RUNX2, and RUNX3 were all increased in most cancers compared with normal tissues, especially in leukemia. Moreover, the expression levels of RUNX1, RUNX2, and RUNX3 are also highly expressed in almost all cancer cell lines, particularly in acute myeloid leukemia (AML) cell lines, analyzed by Cancer Cell Line Encyclopedia (CCLE) and European Bioinformatics Institute (EMBL-EBI) databases. Further, the LinkedOmics and GEPIA databases were used to evaluate the prognostic values. In survival analyses based on LinkedOmics, higher expression of RUNX1 and RUNX2 indicated a better overall survival (OS), but with no significance, whereas increased RUNX3 revealed a poor OS in leukemia. In addition, the GEPIA dataset was also used to perform survival analyses, and results manifested that the expression of RUNX1 and RUNX2 had no remarkable correction with OS in leukemia, but it showed highly expressed RUNX3 was significantly related with poor OS in leukemia. In conclusion, the RUNX family showed significant expression differences between cancer and normal tissues, especially leukemia, and RUNX3 could be a promising prognostic biomarker for leukemia. Keywords: Runt-related transcription factor, leukemia, ONCOMINE, Cancer Cell Line Encyclopedia
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- 2019
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6. The lncRNA PDIA3P Interacts with miR-185-5p to Modulate Oral Squamous Cell Carcinoma Progression by Targeting Cyclin D2
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Cheng-Cao Sun, Ling Zhang, Guang Li, Shu-Jun Li, Zhen-Long Chen, Yun-Feng Fu, Feng-Yun Gong, Tao Bai, Ding-Yu Zhang, Qing-Ming Wu, and De-Jia Li
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protein disulfide isomerase family A member 3 pseudogene 1 ,PDIA3P ,miR-185-5p ,cyclin D2 ,oral squamous cell carcinoma ,OSCC ,tumorigenesis ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Long noncoding RNAs (lncRNAs) are emerging as important regulators during tumorigenesis by serving as competing endogenous RNAs (ceRNAs). In this study, the qRT-PCR results indicated that the lncRNA protein disulfide isomerase family A member 3 pseudogene 1 (PDIA3P) was overexpressed in oral squamous cell carcinoma (OSCC) and decreased the survival rate of OSCC patients. CCK-8 and clonal colony formation assays were used to detect the effects of PDIA3P on proliferation. Results revealed that silencing PDIA3P by small interfering RNA (siRNA) inhibited OSCC cell proliferation and repressed tumor growth and reduced the expression of proliferation antigen Ki-67 in vivo. Furthermore, the interaction between PDIA3P and miRNAs was then analyzed by qRT-PCR and luciferase reporter gene assay. We found that PDIA3P negatively regulated miR-185-5p in OSCC cells. Simultaneously, we found that silencing PDIA3P by siRNA suppressed proliferation via miR-185-5p in OSCC cells. Moreover, silencing PDIA3P by siRNA inhibited CCND2 protein (no influence on mRNA levels) expression via miR-185-5p in OSCC cells, and CCND2 facilitated cell proliferation of SCC4 and SCC15 cells induced by sh-PDIA3P#1. Therefore, our study demonstrated that PDIA3P may be a therapeutic target for the treatment of OSCC.
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- 2017
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7. miR-206/133b Cluster: A Weapon against Lung Cancer?
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Jing-Yu Pan, Cheng-Cao Sun, Zhuo-Yue Bi, Zhen-Long Chen, Shu-Jun Li, Qing-Qun Li, Yu-Xuan Wang, Yong-Yi Bi, and De-Jia Li
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Therapeutics. Pharmacology ,RM1-950 - Abstract
Lung cancer is a deadly disease that ends numerous lives around the world. MicroRNAs (miRNAs) are a group of non-coding RNAs involved in a variety of biological processes, such as cell growth, organ development, and tumorigenesis. The miR-206/133b cluster is located on the human chromosome 6p12.2, which is essential for growth and rebuilding of skeletal muscle. The miR-206/133b cluster has been verified to be dysregulated and plays a crucial role in lung cancer. miR-206 and miR-133b participate in lung tumor cell apoptosis, proliferation, migration, invasion, angiogenesis, drug resistance, and cancer treatment. The mechanisms are sophisticated, involving various target genes and molecular pathways, such as MET, EGFR, and the STAT3/HIF-1α/VEGF signal pathway. Hence, in this review, we summarize the role and potential mechanisms of the miR-206/133b cluster in lung cancer. Keywords: lung cancer, miR-206/133b cluster, miR-206, miR-133b
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- 2017
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8. miR-134: A Human Cancer Suppressor?
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Jing-Yu Pan, Feng Zhang, Cheng-Cao Sun, Shu-Jun Li, Guang Li, Feng-Yun Gong, Tao Bo, Jing He, Rui-Xi Hua, Wei-Dong Hu, Zhan-Peng Yuan, Xin Wang, Qi-Qiang He, and De-Jia Li
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Therapeutics. Pharmacology ,RM1-950 - Abstract
MicroRNAs (miRNAs) are small noncoding RNAs approximately 20–25 nt in length, which play crucial roles through directly binding to corresponding 3′ UTR of targeted mRNAs. It has been reported that miRNAs are involved in numerous of diseases, including cancers. Recently, miR-134 has been identified to dysregulate in handles of human cancers, such as lung cancer, glioma, breast cancer, colorectal cancer, and so on. Increasing evidence indicates that miR-134 is essential for human carcinoma and participates in tumor cell proliferation, apoptosis, invasion and metastasis, drug resistance, as well as cancer diagnosis, treatment, and prognosis. Nevertheless, its roles in human cancer are still ambiguous, and its mechanisms are sophisticated as well, referring to a variety of targets and signal pathways, such as STAT5B, KRAS, MAPK/ERK signal pathway, Notch pathway, etc. Herein, we review the crucial roles of miR-134 in scores of human cancers via analyzing latest investigations, which might provide evidence for cancer diagnose, treatment, prognosis, or further investigations. Keywords: miR-134, human cancer, microRNA
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- 2017
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9. The Novel miR-9600 Suppresses Tumor Progression and Promotes Paclitaxel Sensitivity in Non–small-cell Lung Cancer Through Altering STAT3 Expression
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Cheng-Cao Sun, Shu-Jun Li, Feng Zhang, Ya-Dong Zhang, Zhen-Yu Zuo, Yong-Yong Xi, Liang Wang, and De-Jia Li
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drug resistance ,miR-9600 ,non–small-cell lung cancer ,STAT3 ,tumorigenesis ,Therapeutics. Pharmacology ,RM1-950 - Abstract
MicroRNAs have been identified to be involved in center stage of cancer biology. They accommodate cell proliferation and migration by negatively regulate gene expression either by hampering the translation of targeted mRNAs or by promoting their degradation. We characterized and identified the novel miR-9600 and its target in human non–small-cell lung cancer (NSCLC). Our results demonstrated that the miR-9600 were downregulated in NSCLC tissues and cells. It is confirmed that signal transducer and activator of transcription 3 (STAT3), a putative target gene, is directly inhibited by miR-9600. The miR-9600 markedly suppressed the protein expression of STAT3, but with no significant influence in corresponding mRNA levels, and the direct combination of miR-9600 and STAT3 was confirmed by a luciferase reporter assay. miR-9600 inhibited cell growth, hampered expression of cell cycle-related proteins and inhibited cell migration and invasion in human NSCLC cell lines. Further, miR-9600 significantly suppressed tumor growth in nude mice. Similarly, miR-9600 impeded tumorigenesis and metastasis through directly targeting STAT3. Furthermore, we identified that miR-9600 augmented paclitaxel and cisplatin sensitivity by downregulating STAT3 and promoting chemotherapy-induced apoptosis. These data demonstrate that miR-9600 might be a useful and novel therapeutic target for NSCLC.
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- 2016
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10. Long Intergenic Noncoding RNA 00511 Acts as an Oncogene in Non–small-cell Lung Cancer by Binding to EZH2 and Suppressing p57
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Cheng-Cao Sun, Shu-Jun Li, Guang Li, Rui-Xi Hua, Xu-Hong Zhou, and De-Jia Li
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enhancer of zeste homolog 2 ,long noncoding RNA LINC00511 ,p57 ,non–small-cell lung cancer ,polycomb repressive complex 2 ,tumorigenesis ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Long noncoding RNAs (lncRNAs) play crucial roles in carcinogenesis. However, the function and mechanism of lncRNAs in human non–small-cell lung cancer (NSCLC) are still remaining largely unknown. Long intergenic noncoding RNA 00511 (LINC00511) has been found to be upregulated and acts as an oncogene in breast cancer, but little is known about its expression pattern, biological function and underlying mechanism in NSCLC. Herein, we identified LINC00511 as an oncogenic lncRNA by driving tumorigenesis in NSCLC. We found LINC00511 was upregulated and associated with oncogenesis, tumor size, metastasis, and poor prognosis in NSCLC. Moreover, LINC00511 affected cell proliferation, invasiveness, metastasis, and apoptosis in multiple NSCLC cell lines. Mechanistically, LINC00511 bound histone methyltransferase enhancer of zeste homolog 2 ((EZH2, the catalytic subunit of the polycomb repressive complex 2 (PRC2), a highly conserved protein complex that regulates gene expression by methylating lysine 27 on histone H3), and acted as a modular scaffold of EZH2/PRC2 complexes, coordinated their localization, and specified the histone modification pattern on the target genes, including p57, and consequently altered NSCLC cell biology. Thus, LINC00511 is mechanistically, functionally, and clinically oncogenic in NSCLC. Targeting LINC00511 and its pathway may be meaningful for treating patients with NSCLC.
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- 2016
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11. The lncRNA H19 alleviates muscular dystrophy by stabilizing dystrophin
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Deqiang Sun, Jin Li, Zhao Zhang, Zhen Xing, Zilong Zhao, Sergey D. Egranov, Chunru Lin, Ping Zhang, Ke Liang, Yajuan Li, Jean J. Kim, Qingsong Hu, Lisa Huang, Leng Han, Cheng-Cao Sun, Yutao Xi, Abid Farida, Yaohua Zhang, Jie Cheng, Jianbo Wu, Tina K. Nguyen, Liuqing Yang, Mien Chie Hung, Radbod Darabi, and David H. Hawke
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Male ,lncRNA mimics ,Oligonucleotides ,Muscle Proteins ,Muscular Dystrophies ,Tripartite Motif Proteins ,Dystrophin ,0302 clinical medicine ,Myocytes, Cardiac ,Enzyme Inhibitors ,Muscular dystrophy ,0303 health sciences ,Agrin ,biology ,Protein Stability ,Cardiac muscle ,musculoskeletal system ,Ubiquitin ligase ,Cell biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Female ,RNA, Long Noncoding ,Cardiomyopathies ,Half-Life ,Niacinamide ,musculoskeletal diseases ,congenital, hereditary, and neonatal diseases and abnormalities ,Ubiquitin-Protein Ligases ,Induced Pluripotent Stem Cells ,Protein degradation ,Article ,Cell Line ,03 medical and health sciences ,Muscle Dystrophy ,medicine ,Animals ,Humans ,Muscle Strength ,Muscle, Skeletal ,030304 developmental biology ,H19 ,business.industry ,Ubiquitination ,Skeletal muscle ,E3 ligase inhibitor ,Cell Biology ,medicine.disease ,Mice, Mutant Strains ,Exon skipping ,Mice, Inbred C57BL ,Disease Models, Animal ,Mutation ,Proteolysis ,Mice, Inbred mdx ,biology.protein ,TRIM63 ,business ,Antipyrine ,Long noncoding RNA - Abstract
Dystrophin proteomic regulation in muscular dystrophies (MDs) remains unclear. We report that a long noncoding RNA (lncRNA), H19, associates with dystrophin and inhibits E3-ligase-dependent polyubiquitination at Lys 3584 (referred to as Ub-DMD) and its subsequent protein degradation. In-frame deletions in BMD and a DMD non-silent mutation (C3340Y) resulted in defects in the ability of the protein to interact with H19, which caused elevated Ub-DMD levels and dystrophin degradation. Dmd C3333Y mice exhibited progressive MD, elevated serum creatine kinase, heart dilation, blood vessel irregularity and respiratory failure with concurrently reduced dystrophin and increased Ub-DMD status. H19 RNA oligonucleotides conjugated with agrin (AGR–H19) and nifenazone competed with or inhibited TRIM63. Dmd C3333Y animals, induced-pluripotent-stem-cell-derived skeletal muscle cells from patients with Becker MD and mdx mice subjected to exon skipping exhibited inhibited dystrophin degradation, preserved skeletal and cardiac muscle histology, and improved strength and heart function following AGR–H19 or nifenazone treatment. Our study paves the way for meaningful targeted therapeutics for Becker MD and for certain patients with Duchenne MD. Zhang et al. report that the lncRNA H19 stabilizes dystrophin by competing with the ubiquitin E3 ligase TRIM63 for association with dystrophin, thereby alleviating muscular dystrophies.
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- 2020
12. Comprehensive landscape of extracellular vesicle-derived RNAs in cancer initiation, progression, metastasis and cancer immunology
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Qi-qiang He, Zhuoyue Bi, Wei Zhu, Yongyi Bi, Cong Liu, Jian Zhang, Cheng-Cao Sun, Lin-Lin Li, Wei Hu, Han Zhang, Qun Zhou, Feng Zhang, Hui-Min Yang, Gong-Jun Tan, Yang-Yi-Yan Song, and De-Jia Li
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0301 basic medicine ,Cancer Research ,Micro RNA ,RNA, Untranslated ,Review ,Biology ,Exosome ,lcsh:RC254-282 ,Extracellular Vesicles ,03 medical and health sciences ,0302 clinical medicine ,Microvesicle ,Neoplasms ,microRNA ,Biomarkers, Tumor ,Animals ,Humans ,RNA, Messenger ,Neoplasm Metastasis ,Premetastatic niche ,Circular RNA ,Cancer ,Cancer immunology ,Tumor microenvironment ,Extracellular vesicle ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Long non-coding RNA ,Microvesicles ,Cell biology ,MicroRNAs ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Disease Progression ,Molecular Medicine - Abstract
Extracellular vesicles (EVs), a class of heterogeneous membrane vesicles, are generally divided into exosomes and microvesicles on basis of their origination from the endosomal membrane or the plasma membrane, respectively. EV-mediated bidirectional communication among various cell types supports cancer cell growth and metastasis. EVs derived from different cell types and status have been shown to have distinct RNA profiles, comprising messenger RNAs and non-coding RNAs (ncRNAs). Recently, ncRNAs have attracted great interests in the field of EV-RNA research, and growing numbers of ncRNAs ranging from microRNAs to long ncRNAs have been investigated to reveal their specific functions and underlying mechanisms in the tumor microenvironment and premetastatic niches. Emerging evidence has indicated that EV-RNAs are essential functional cargoes in modulating hallmarks of cancers and in reciprocal crosstalk within tumor cells and between tumor and stromal cells over short and long distance, thereby regulating the initiation, development and progression of cancers. In this review, we discuss current findings regarding EV biogenesis, release and interaction with target cells as well as EV-RNA sorting, and highlight biological roles and molecular mechanisms of EV-ncRNAs in cancer biology.
- Published
- 2020
13. Correction to: FOXC1-mediated LINC00301 facilitates tumor progression and triggers an immune-suppressing microenvironment in non-small cell lung cancer by regulating the HIF1α pathway
- Author
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Han Zhang, Shu-Jun Li, Jian Zhang, Shao-Xin Huang, Wei Zhu, Juan Wang, Cheng-Cao Sun, De-Jia Li, Yue Zhuo, Wei Hu, Qi-Qiang He, and Yu Zhang
- Subjects
0301 basic medicine ,lcsh:QH426-470 ,T cell ,non-small cell lung cancer (NSCLC) ,lcsh:Medicine ,medicine.disease_cause ,03 medical and health sciences ,0302 clinical medicine ,Genetics ,medicine ,Electrophoretic mobility shift assay ,Molecular Biology ,Transcription factor ,Genetics (clinical) ,Chemistry ,Competing endogenous RNA ,Cell growth ,lcsh:R ,medicine.disease ,lcsh:Genetics ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Cancer research ,Molecular Medicine ,Carcinogenesis ,Chromatin immunoprecipitation - Abstract
Long non-coding RNAs (lncRNAs) are extensively intricate in the tumorigenesis and metastasis of various cancer types. Nevertheless, the detailed molecular mechanisms of lncRNA in non-small cell lung cancer (NSCLC) still remain mainly undetermined. qPCR was performed to verify LINC00301 expression in NSCLC clinical specimens or cell lines. Fluorescence in situ hybridization (FISH) was conducted to identify the localization of LINC00301 in NSCLC cells. Chromatin immunoprecipitation (ChIP) was subjected to validate the binding activity between FOXC1 and LINC00301 promoters. RNA immunoprecipitation (RIP) was performed to explore the binding activity between LINC00301 and EZH2. RNA pull-down followed by dot-blot, protein domain mapping, and RNA electrophoresis mobility shift assay (EMSA) were conducted to identify the detailed binding regions between LINC00301 and EZH2. Alpha assay was conducted to quantitatively assess the interaction between LINC00301 and EZH2. LINC00301 is highly expressed in NSCLC and closely corelated to its prognosis by analyzing the relationship between differentially expressed lncRNAs and prognosis in NSCLC samples. in vitro and in vivo experiments revealed that LINC00301 facilitates cell proliferation, releases NSCLC cell cycle arrest, promotes cell migration and invasion, and suppresses cell apoptosis in NSCLC. In addition, LINC00301 increases regulatory T cell (Treg) while decreases CD8+ T cell population in LA-4/SLN-205-derived tumors through targeting TGF-β. The transcription factor FOXC1 mediates LINC00301 expression in NSCLC. Bioinformatics prediction and in vitro experiments indicated that LINC00301 (83–123 nucleotide [nt]) can directly bind to the enhancer of zeste homolog 2 (EZH2) (612–727 amino acid [aa]) to promote H3K27me3 at the ELL protein-associated factor 2 (EAF2) promoter. EAF2 directly binds and stabilizes von Hippel–Lindau protein (pVHL), so downregulated EAF2 augments hypoxia-inducible factor 1 α (HIF1α) expression by regulating pVHL in NSCLC cells. Moreover, we also found that LINC00301 could function as a competing endogenous RNA (ceRNA) against miR-1276 to expedite HIF1α expression in the cytoplasm of NSCLC cells. In summary, our present research revealed the oncogenic roles of LINC00301 in clinical specimens as well as cellular and animal experiments, illustrating the potential roles and mechanisms of the FOXC1/LINC00301/EZH2/EAF2/pVHL/HIF1α and FOXC1/LINC00301/miR-1276/HIF1α pathways, which provides novel insights and potential theraputic targets to NSCLC.
- Published
- 2021
14. Retraction Notice to: Comprehensive Analysis of the Expression and Prognosis for E2Fs in Human Breast Cancer
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Cheng-Cao Sun, Shu-Jun Li, Wei Hu, Jian Zhang, Qun Zhou, Cong Liu, Lin-Lin Li, Yi-Yan Songyang, Feng Zhang, Zhen-Long Chen, Guang Li, Zhuo-Yue Bi, Yong-Yi Bi, Feng-Yun Gong, Tao Bo, Zhan-Peng Yuan, Wei-Dong Hu, Bo-Tao Zhan, Qian Zhang, Qi-Qiang He, and De-Jia Li
- Subjects
Pharmacology ,Drug Discovery ,Genetics ,Molecular Medicine ,Molecular Biology - Published
- 2022
15. Correction to: LncRNA PVT1 up-regulation is a poor prognosticator and serves as a therapeutic target in esophageal adenocarcinoma
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Yuan Li, Ying Wang, Longfei Huo, Manoop S. Bhutani, A. Robert MacLeod, Ailing W. Scott, Melissa Pool Pizzi, Guangchun Han, Jeffrey H. Lee, Zhenning Wang, Christopher P. Vellano, Cheng-Cao Sun, Chunru Lin, Liuqing Yang, Youngsoo Kim, Shumei Song, Jiankang Jin, Yan Xu, Lang Ma, Brian Weston, Jaffer A. Ajani, and Linghua Wang
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Oncology ,Cancer Research ,medicine.medical_specialty ,Esophageal Neoplasms ,MEDLINE ,Esophageal adenocarcinoma ,Adenocarcinoma ,Biology ,lcsh:RC254-282 ,Models, Biological ,Mice ,Text mining ,Cell Movement ,Cell Line, Tumor ,Internal medicine ,Biomarkers, Tumor ,medicine ,Animals ,Humans ,Adaptor Proteins, Signal Transducing ,Cell Proliferation ,business.industry ,Correction ,YAP-Signaling Proteins ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Prognosis ,PVT1 ,Gene Expression Regulation, Neoplastic ,Disease Models, Animal ,Molecular Medicine ,RNA, Long Noncoding ,business ,Transcription Factors - Abstract
PVT1 has emerged as an oncogene in many tumor types. However, its role in Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) is unknown. The aim of this study was to assess the role of PVT1 in BE/EAC progression and uncover its therapeutic value against EAC.PVT1 expression was assessed by qPCR in normal, BE, and EAC tissues and statistical analysis was performed to determine the association of PVT1 expression and EAC (stage, metastases, and survival). PVT1 antisense oligonucleotides (ASOs) were tested for their antitumor activity in vitro and in vivo.PVT1 expression was up-regulated in EACs compared with paired BEs, and normal esophageal tissues. High expression of PVT1 was associated with poor differentiation, lymph node metastases, and shorter survival. Effective knockdown of PVT1 in EAC cells using PVT1 ASOs resulted in decreased cell proliferation, invasion, colony formation, tumor sphere formation, and reduced proportion of ALDH1A1Our results provide strong evidence that PVT1 confers an aggressive phenotype to EAC and is a poor prognosticator. Combined targeting of PVT1 and YAP1 provided the highest therapeutic index and represents a novel therapeutic strategy.
- Published
- 2021
16. Mechanism of efficient double-strand break repair by a long non-coding RNA
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Shujuan Fang, Ruiqiong Ye, Aleš Hnízda, Roopa Thapar, Isaac Forrester, Chunru Lin, Linda Lee, Susan P. Lees-Miller, Heather Villarreal, Su S. Maw, Terence R. Strick, Miaw Sheue Tsai, Anthony J. Davis, Michal Hammel, Cheng-Cao Sun, Jing L. Wang, John A. Tainer, Shikang Liang, Tom L. Blundell, Ke Liang, Liang, Shikang [0000-0002-6930-7882], Blundell, Tom [0000-0002-2708-8992], and Apollo - University of Cambridge Repository
- Subjects
Ku80 ,DNA End-Joining Repair ,DNA repair ,AcademicSubjects/SCI00010 ,Biology ,Genome Integrity, Repair and Replication ,chemistry.chemical_compound ,03 medical and health sciences ,Double-Stranded ,Information and Computing Sciences ,Genetics ,Humans ,DNA Breaks, Double-Stranded ,Ku Autoantigen ,030304 developmental biology ,Cancer ,Ku70 ,0303 health sciences ,030302 biochemistry & molecular biology ,DNA Breaks ,RNA ,Biological Sciences ,Double Strand Break Repair ,Long non-coding RNA ,Cell biology ,DNA-Binding Proteins ,chemistry ,Hela Cells ,RNA, Long Noncoding ,Long Noncoding ,Protein Multimerization ,Corrigendum ,DNA ,Environmental Sciences ,HeLa Cells ,Protein Binding ,Developmental Biology - Abstract
Mechanistic studies in DNA repair have focused on roles of multi-protein DNA complexes, so how long non-coding RNAs (lncRNAs) regulate DNA repair is less well understood. Yet, lncRNA LINP1 is over-expressed in multiple cancers and confers resistance to ionizing radiation and chemotherapeutic drugs. Here, we unveil structural and mechanistic insights into LINP1’s ability to facilitate non-homologous end joining (NHEJ). We characterized LINP1 structure and flexibility and analyzed interactions with the NHEJ factor Ku70/Ku80 (Ku) and Ku complexes that direct NHEJ. LINP1 self-assembles into phase-separated condensates via RNA–RNA interactions that reorganize to form filamentous Ku-containing aggregates. Structured motifs in LINP1 bind Ku, promoting Ku multimerization and stabilization of the initial synaptic event for NHEJ. Significantly, LINP1 acts as an effective proxy for PAXX. Collective results reveal how lncRNA effectively replaces a DNA repair protein for efficient NHEJ with implications for development of resistance to cancer therapy.
- Published
- 2021
17. Targeting TFAP2C/PDCD6 Pathway by lncRNA PP7080 Expedites Tumorigenesis and Contributes to an Immunosuppressive Tumor Microenvironment in Non‐Small Cell Lung Cancer
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Yue Zhuo, Wei Hu, Mei‐Juan Liao, Jia‐Hao Chen, Jian Zhang, Juan Wang, Yu Zhang, Fa‐Xue Zhang, Yu‐Fan Shi, Hui‐Ling Qian, Shu‐Jun Li, and Cheng‐Cao Sun
- Subjects
Pharmacology ,Biochemistry (medical) ,Pharmaceutical Science ,Medicine (miscellaneous) ,Pharmacology (medical) ,Genetics (clinical) - Published
- 2022
18. Medical Staff Cases Infected with COVID-19 in Wuhan, China
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Cheng-Cao Sun, Liang Wang, and Dejia Li
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medicine.medical_specialty ,Medical staff ,Coronavirus disease 2019 (COVID-19) ,Transmission (medicine) ,business.industry ,viruses ,Disease ,Disease cluster ,Virus ,Emergency medicine ,Epidemiology ,medicine ,Infection control ,business - Abstract
We reported a cluster of 6 suspected medical staff cases infected with 2019 novel coronavirus disease (COVID-19) during January - March 2020. It described an epidemiological and clinical pattern with atypical presentation. To reduce the transmission levels of the virus in medical staff, we recommend appropriate precautions including viral nucleic acid detection and hospital infection control.
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- 2020
19. Analysis of clinical characteristics of SARS-CoV-2 infected cases: a retrospective study of medical records
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Jian Zhang, Lian Lu, Wei Zhu, Qi-Qiang He, Wei Hu, Han Zhang, De-Jia Li, and Cheng-Cao Sun
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medicine.medical_specialty ,business.industry ,Medical record ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Emergency medicine ,Medicine ,Retrospective cohort study ,business - Abstract
Objectives In order to identify the clinical characteristics of patients with Corona Virus Disease 2019 (COVID-19) and find out the characteristic effects of 2019 New Coronavirus (SARS-CoV-2) infection on changes in clinical and laboratory data. Patients and methods From January 22 to February 13, 2020, we enrolled consecutive patients with acute respiratory tract symptoms admitted to a hospital (Ezhou, Hubei, China). For different data types t-test, the variables associated with the diagnosis of COVID-19 were compared by chi-square test and u-test, the statistically significant variables (P-valueResults 62 (77.5%) confirmed cases and 18 (22.5%) negative cases were confirmed by SARS-CoV-2 nucleic acid test. Epidemiological investigation and statistical analysis were carried out on the clinical and laboratory data of all suspected cases of COVID-19, the specific indicators were found, and the clinical characteristics of COVID-19 were described. Compared with the patients with negative nucleic acid test, the patients with positive nucleic acid test showed shorter time of onset of symptoms, higher plasma CO2 level, lower eosinophil ratio, lower platelet count and hematocrit, lower serum sodium level, higher serum creatinine, higher blood urea and plasma albumin levels (all PConclusions we argue that the SARS-CoV-2 infection can cause multiple organ damage to the heart, liver, kidney and bone marrow other than lung injury.
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- 2020
20. FOXC1-mediated LINC00301 facilitates tumor progression and triggers an immune-suppressing microenvironment in non-small cell lung cancer by regulating the HIF1α pathway
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Cheng-Cao Sun, Wei Zhu, Shu-Jun Li, Wei Hu, Jian Zhang, Yue Zhuo, Han Zhang, Juan Wang, Yu Zhang, Shao-Xin Huang, Qi-Qiang He, and De-Jia Li
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0301 basic medicine ,Lung Neoplasms ,lcsh:QH426-470 ,Enhancer of zeste homolog 2 (EZH2) ,lcsh:Medicine ,Hypoxia-inducible factor 1 α (HIF1α) ,Non-small cell lung cancer (NSCLC) ,Regulatory T cells (Treg) ,Histones ,Immunomodulation ,03 medical and health sciences ,Mice ,0302 clinical medicine ,T-Lymphocyte Subsets ,ELL protein-associated factor 2 (EAF2) ,Carcinoma, Non-Small-Cell Lung ,Cell Line, Tumor ,Genetics ,Tumor Microenvironment ,Animals ,Humans ,Nucleotide Motifs ,Promoter Regions, Genetic ,Molecular Biology ,Genetics (clinical) ,Binding Sites ,Research ,lcsh:R ,Cell Cycle ,Correction ,Forkhead Transcription Factors ,DNA Methylation ,Hypoxia-Inducible Factor 1, alpha Subunit ,Prognosis ,Gene Expression Regulation, Neoplastic ,lcsh:Genetics ,Disease Models, Animal ,030104 developmental biology ,030220 oncology & carcinogenesis ,LINC00301 ,Tumorigenesis ,Disease Progression ,Molecular Medicine ,RNA, Long Noncoding ,miR-1276 ,Protein Binding ,Signal Transduction - Abstract
Background Long non-coding RNAs (lncRNAs) are extensively intricate in the tumorigenesis and metastasis of various cancer types. Nevertheless, the detailed molecular mechanisms of lncRNA in non-small cell lung cancer (NSCLC) still remain mainly undetermined. Methods qPCR was performed to verify LINC00301 expression in NSCLC clinical specimens or cell lines. Fluorescence in situ hybridization (FISH) was conducted to identify the localization of LINC00301 in NSCLC cells. Chromatin immunoprecipitation (ChIP) was subjected to validate the binding activity between FOXC1 and LINC00301 promoters. RNA immunoprecipitation (RIP) was performed to explore the binding activity between LINC00301 and EZH2. RNA pull-down followed by dot-blot, protein domain mapping, and RNA electrophoresis mobility shift assay (EMSA) were conducted to identify the detailed binding regions between LINC00301 and EZH2. Alpha assay was conducted to quantitatively assess the interaction between LINC00301 and EZH2. Results LINC00301 is highly expressed in NSCLC and closely corelated to its prognosis by analyzing the relationship between differentially expressed lncRNAs and prognosis in NSCLC samples. in vitro and in vivo experiments revealed that LINC00301 facilitates cell proliferation, releases NSCLC cell cycle arrest, promotes cell migration and invasion, and suppresses cell apoptosis in NSCLC. In addition, LINC00301 increases regulatory T cell (Treg) while decreases CD8+ T cell population in LA-4/SLN-205-derived tumors through targeting TGF-β. The transcription factor FOXC1 mediates LINC00301 expression in NSCLC. Bioinformatics prediction and in vitro experiments indicated that LINC00301 (83–123 nucleotide [nt]) can directly bind to the enhancer of zeste homolog 2 (EZH2) (612–727 amino acid [aa]) to promote H3K27me3 at the ELL protein-associated factor 2 (EAF2) promoter. EAF2 directly binds and stabilizes von Hippel–Lindau protein (pVHL), so downregulated EAF2 augments hypoxia-inducible factor 1 α (HIF1α) expression by regulating pVHL in NSCLC cells. Moreover, we also found that LINC00301 could function as a competing endogenous RNA (ceRNA) against miR-1276 to expedite HIF1α expression in the cytoplasm of NSCLC cells. Conclusions In summary, our present research revealed the oncogenic roles of LINC00301 in clinical specimens as well as cellular and animal experiments, illustrating the potential roles and mechanisms of the FOXC1/LINC00301/EZH2/EAF2/pVHL/HIF1α and FOXC1/LINC00301/miR-1276/HIF1α pathways, which provides novel insights and potential theraputic targets to NSCLC.
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- 2019
21. LncRNA PVT1 up-regulation is a poor prognosticator and serves as a therapeutic target in esophageal adenocarcinoma
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Longfei Huo, Shumei Song, A. Robert MacLeod, Guangchun Han, Liuqing Yang, Linghua Wang, Melissa Pool Pizzi, Chunru Lin, Zhenning Wang, Yuan Li, Yan Xu, Jaffer A. Ajani, Manoop S. Bhutani, Ailing W. Scott, Christopher P. Vellano, Cheng-Cao Sun, Lang Ma, Brian Weston, Youngsoo Kim, Jeffrey H. Lee, Jiankang Jin, and Ying Wang
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0301 basic medicine ,Cancer Research ,YAP1 ,lcsh:RC254-282 ,03 medical and health sciences ,0302 clinical medicine ,Therapeutic index ,In vivo ,medicine ,PVT1 ,Lymph node ,Lnc RNA ,Gene knockdown ,Antisense oligonucleotides ,Oncogene ,biology ,Research ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,ALDH1A1 ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,biology.protein ,Molecular Medicine ,Esophageal adenocarcinoma - Abstract
Background PVT1 has emerged as an oncogene in many tumor types. However, its role in Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC) is unknown. The aim of this study was to assess the role of PVT1 in BE/EAC progression and uncover its therapeutic value against EAC. Methods PVT1 expression was assessed by qPCR in normal, BE, and EAC tissues and statistical analysis was performed to determine the association of PVT1 expression and EAC (stage, metastases, and survival). PVT1 antisense oligonucleotides (ASOs) were tested for their antitumor activity in vitro and in vivo. Results PVT1 expression was up-regulated in EACs compared with paired BEs, and normal esophageal tissues. High expression of PVT1 was associated with poor differentiation, lymph node metastases, and shorter survival. Effective knockdown of PVT1 in EAC cells using PVT1 ASOs resulted in decreased cell proliferation, invasion, colony formation, tumor sphere formation, and reduced proportion of ALDH1A1+ cells. Mechanistically, we discovered mutual regulation of PVT1 and YAP1 in EAC cells. Inhibition of PVT1 by PVT1 ASOs suppressed YAP1 expression through increased phosphor-LATS1and phosphor-YAP1 while knockout of YAP1 in EAC cells significantly suppressed PVT1 levels indicating a positive regulation of PVT1 by YAP1. Most importantly, we found that targeting both PVT1 and YAP1 using their specific ASOs led to better antitumor activity in vitro and in vivo. Conclusions Our results provide strong evidence that PVT1 confers an aggressive phenotype to EAC and is a poor prognosticator. Combined targeting of PVT1 and YAP1 provided the highest therapeutic index and represents a novel therapeutic strategy.
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- 2019
22. Long intergenic non-protein coding RNA 319 aggravates lung adenocarcinoma carcinogenesis by modulating miR-450b-5p/EZH2
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Jun-Bo Yang, Jun Jiao, Bo-Tao Zhan, Cheng-Cao Sun, Hua Zhao, Bin He, Zengwang Zhang, Jia-Jun Chen, Shi-Hui Xia, and Hao Zhang
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0301 basic medicine ,Lung Neoplasms ,Carcinogenesis ,Adenocarcinoma of Lung ,Adenocarcinoma ,Biology ,medicine.disease_cause ,03 medical and health sciences ,0302 clinical medicine ,Intergenic region ,Cell Line, Tumor ,Genetics ,medicine ,Humans ,Enhancer of Zeste Homolog 2 Protein ,Cell Proliferation ,Protein coding ,Lung ,EZH2 ,RNA ,General Medicine ,respiratory system ,medicine.disease ,In vitro ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,030104 developmental biology ,medicine.anatomical_structure ,A549 Cells ,030220 oncology & carcinogenesis ,Disease Progression ,Cancer research ,DNA, Intergenic ,RNA, Long Noncoding ,Signal Transduction - Abstract
Growing evidence shows that long non-coding RNAs (lncRNAs) have been wildly verified to modulate multiple tumorigenesis, especially lung adenocarcinoma. In present study, we aim to investigate the role of lncRNA LINC00319 in the lung adenocarcinoma carcinogenesis. We observed that increased expression of LINC00319 in lung adenocarcinoma tissues and cells in comparison to their corresponding controls. Moreover, the aberrant overexpression of LINC00319 indicated the poor prognosis of lung adenocarcinoma patients. Silence of LINC00319 was able to repress lung adenocarcinoma cell growth in vitro. Rescue assay was performed to further confirm that LINC00319 contributed to lung adenocarcinoma progression by regulating miR-450b-5p/EZH2 signal pathway. Taken together, our study discovered the oncogenic role of LINC00319 in clinical specimens and cellular experiments, showing the potential LINC00319/miR-450b-5p/EZH2 pathway. This results and findings provide a novel insight for lung adenocarcinoma tumorigenesis.
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- 2018
23. The lncRNA PDIA3P Interacts with miR-185-5p to Modulate Oral Squamous Cell Carcinoma Progression by Targeting Cyclin D2
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Ding-Yu Zhang, Feng-Yun Gong, Cheng-Cao Sun, Ling Zhang, Dejia Li, Zhen-Long Chen, Qing-Ming Wu, Yunfeng Fu, Tao Bai, Shu-Jun Li, and Guang Li
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0301 basic medicine ,Small interfering RNA ,cyclin D2 ,Biology ,medicine.disease_cause ,03 medical and health sciences ,0302 clinical medicine ,Cyclin D2 ,Antigen ,Drug Discovery ,microRNA ,medicine ,Gene silencing ,Cell growth ,Competing endogenous RNA ,lcsh:RM1-950 ,PDIA3P ,miR-185-5p ,oral squamous cell carcinoma ,stomatognathic diseases ,protein disulfide isomerase family A member 3 pseudogene 1 ,tumorigenesis ,030104 developmental biology ,lcsh:Therapeutics. Pharmacology ,030220 oncology & carcinogenesis ,Cancer research ,Molecular Medicine ,Original Article ,OSCC ,Carcinogenesis - Abstract
Long noncoding RNAs (lncRNAs) are emerging as important regulators during tumorigenesis by serving as competing endogenous RNAs (ceRNAs). In this study, the qRT-PCR results indicated that the lncRNA protein disulfide isomerase family A member 3 pseudogene 1 (PDIA3P) was overexpressed in oral squamous cell carcinoma (OSCC) and decreased the survival rate of OSCC patients. CCK-8 and clonal colony formation assays were used to detect the effects of PDIA3P on proliferation. Results revealed that silencing PDIA3P by small interfering RNA (siRNA) inhibited OSCC cell proliferation and repressed tumor growth and reduced the expression of proliferation antigen Ki-67 in vivo. Furthermore, the interaction between PDIA3P and miRNAs was then analyzed by qRT-PCR and luciferase reporter gene assay. We found that PDIA3P negatively regulated miR-185-5p in OSCC cells. Simultaneously, we found that silencing PDIA3P by siRNA suppressed proliferation via miR-185-5p in OSCC cells. Moreover, silencing PDIA3P by siRNA inhibited CCND2 protein (no influence on mRNA levels) expression via miR-185-5p in OSCC cells, and CCND2 facilitated cell proliferation of SCC4 and SCC15 cells induced by sh-PDIA3P#1. Therefore, our study demonstrated that PDIA3P may be a therapeutic target for the treatment of OSCC.
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- 2017
24. miR-206/133b Cluster: A Weapon against Lung Cancer?
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Yongyi Bi, Jing-Yu Pan, Shu-Jun Li, Cheng-Cao Sun, Zhen-Long Chen, Zhuoyue Bi, Qing-Qun Li, Yu-Xuan Wang, and Dejia Li
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0301 basic medicine ,Angiogenesis ,Review ,Disease ,medicine.disease_cause ,Bioinformatics ,miR-133b ,03 medical and health sciences ,Drug Discovery ,microRNA ,medicine ,STAT3 ,Lung cancer ,biology ,Cell growth ,miR-206 ,lcsh:RM1-950 ,medicine.disease ,lung cancer ,030104 developmental biology ,lcsh:Therapeutics. Pharmacology ,Apoptosis ,biology.protein ,Cancer research ,Molecular Medicine ,miR-206/133b cluster ,Carcinogenesis - Abstract
Lung cancer is a deadly disease that ends numerous lives around the world. MicroRNAs (miRNAs) are a group of non-coding RNAs involved in a variety of biological processes, such as cell growth, organ development, and tumorigenesis. The miR-206/133b cluster is located on the human chromosome 6p12.2, which is essential for growth and rebuilding of skeletal muscle. The miR-206/133b cluster has been verified to be dysregulated and plays a crucial role in lung cancer. miR-206 and miR-133b participate in lung tumor cell apoptosis, proliferation, migration, invasion, angiogenesis, drug resistance, and cancer treatment. The mechanisms are sophisticated, involving various target genes and molecular pathways, such as MET, EGFR, and the STAT3/HIF-1α/VEGF signal pathway. Hence, in this review, we summarize the role and potential mechanisms of the miR-206/133b cluster in lung cancer. Keywords: lung cancer, miR-206/133b cluster, miR-206, miR-133b
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- 2017
25. Echinocystic acid ameliorates hyperhomocysteinemia-induced vascular endothelial cell injury through regulating NF-κB and CYP1A1
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Cheng‑Cao Sun, Ling Li, Wei‑Na Wang, Yu‑Qing Wang, Yin Li, Dejia Li, and Chuan‑Feng Huang
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0301 basic medicine ,Vitamin ,Cancer Research ,medicine.medical_specialty ,Pathology ,Hyperhomocysteinemia ,echinocystic acid ,vascular endothelial cells ,H&E stain ,Biology ,03 medical and health sciences ,chemistry.chemical_compound ,Immunology and Microbiology (miscellaneous) ,Adventitia ,medicine.artery ,Internal medicine ,medicine ,Vitamin B12 ,hyperhomocysteinemia ,Aorta ,General Medicine ,Articles ,medicine.disease ,Endothelial stem cell ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,chemistry ,Apoptosis ,nuclear factor κB ,cytochrome P450 1A1 - Abstract
The present study investigated the role of echinocystic acid (EA) on the expression of nuclear factor (NF)-κB and cytochrome P450 1A1 (CYP1A1), and aortic morphology, in a rat model of hyperhomocysteinemia (Hhcy). A total of 50 Sprague Dawley rats were randomly divided into five groups as follows: Normal control (NC), model control (MC), vitamin control (VC; folic acid 1 mg/kg + vitamin B2 2 mg/kg + vitamin B12 10u g/kg), EA1 (20 mg/kg EA) and EA2 (40 mg/kg EA). Plasma homocysteine (Hcy) levels were determined via high performance liquid chromatography, and the morphology of the aorta was investigated using hematoxylin and eosin staining. Furthermore, aortic mRNA and protein levels of NF-κB and CYP1A1 were measured using reverse transcription-quantitative polymerase chain reaction analysis and western blotting, respectively. Plasma Hcy levels, and aortic mRNA and protein levels of NF-κB and CYP1A1, were significantly lower in the EA-treated group compared with the MC group (all P
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- 2017
26. CDK3 is a major target of miR-150 in cell proliferation and anti-cancer effect
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Yongyong Xi, Cheng-Cao Sun, Heng Jiang, Qi-qiang He, Dejia Li, Liang Wang, and Feng Zhang
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0301 basic medicine ,Lung Neoplasms ,Carcinogenesis ,Duchenne muscular dystrophy ,Clinical Biochemistry ,Down-Regulation ,Biology ,medicine.disease_cause ,Pathology and Forensic Medicine ,Myoblasts ,Mice ,03 medical and health sciences ,Carcinoma, Non-Small-Cell Lung ,Cell Line, Tumor ,microRNA ,Utrophin ,medicine ,Animals ,Humans ,Amino Acid Sequence ,Molecular Biology ,Cell Proliferation ,Cell growth ,Cyclin-Dependent Kinase 3 ,Cyclin-dependent kinase 3 ,Transfection ,medicine.disease ,Molecular biology ,Up-Regulation ,Gene Expression Regulation, Neoplastic ,Mice, Inbred C57BL ,MicroRNAs ,030104 developmental biology ,Cancer research ,C2C12 - Abstract
MiR-150, a member of small non-coding RNAs, has been proven to dysregulate in different types of tumor and bear on carcinogenesis and cancer prognosis by regulating the expression of a series of gene including utrophin. Given that utrophin can compensate for dystrophin's absence and be regarded as a promising therapeutic target for Duchenne Muscular Dystrophy (DMD), we further detected the deep role of miR-150 in dystrophic muscle. Using a range of bioinformatic, molecular and cell biology techniques, we declared that miR-150 directly targets cyclin-dependent kinase 3 (CDK3) and leads to the regulation of CDK3 gene expression in both muscle-derived and non-muscle cells. The results indicated the expression of miR-150 was upregulated in mdx muscle and closely related to the lower level of CDK3. Transient transfection of miR-150 into cultured C2C12 cells led to significant decrease in cell proliferation, which is partly mediated via the 3'-UTRs of CDK3 mRNA. Targeting of CDK3 could also play a role, at least in part, in the anti-cancer activity suggested for miR-150 in previous studies. Consistently, the analysis of tumor and matched normal lung tissues indicates that miR-150 downregulation in lung tumors correlates with higher CDK3 levels. In addition, miR-150 transfection experiments with cancer-derived cell lines reveal that miR-150-mediated CDK3 suppression directly induces to growth inhibition. Collectively, our results highlight a novel activity for CDK3 in myoblast cell proliferation and confirm CDK3 as a key target that further enhances the tumor suppressor function proposed for miR-150.
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- 2017
27. miR-134: A Human Cancer Suppressor?
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Feng-Yun Gong, Qi-qiang He, Tao Bo, Feng Zhang, Dejia Li, Cheng-Cao Sun, Guang Li, Zhan-Peng Yuan, Jing-Yu Pan, Rui-Xi Hua, Jing He, Shu-Jun Li, Xin Wang, and Wei-Dong Hu
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0301 basic medicine ,Colorectal cancer ,Notch signaling pathway ,Review ,Biology ,miR-134 ,Bioinformatics ,medicine.disease_cause ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Drug Discovery ,microRNA ,medicine ,Lung cancer ,human cancer ,lcsh:RM1-950 ,Cancer ,medicine.disease ,lcsh:Therapeutics. Pharmacology ,030104 developmental biology ,030220 oncology & carcinogenesis ,Molecular Medicine ,KRAS - Abstract
MicroRNAs (miRNAs) are small noncoding RNAs approximately 20–25 nt in length, which play crucial roles through directly binding to corresponding 3′ UTR of targeted mRNAs. It has been reported that miRNAs are involved in numerous of diseases, including cancers. Recently, miR-134 has been identified to dysregulate in handles of human cancers, such as lung cancer, glioma, breast cancer, colorectal cancer, and so on. Increasing evidence indicates that miR-134 is essential for human carcinoma and participates in tumor cell proliferation, apoptosis, invasion and metastasis, drug resistance, as well as cancer diagnosis, treatment, and prognosis. Nevertheless, its roles in human cancer are still ambiguous, and its mechanisms are sophisticated as well, referring to a variety of targets and signal pathways, such as STAT5B, KRAS, MAPK/ERK signal pathway, Notch pathway, etc. Herein, we review the crucial roles of miR-134 in scores of human cancers via analyzing latest investigations, which might provide evidence for cancer diagnose, treatment, prognosis, or further investigations. Keywords: miR-134, human cancer, microRNA
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- 2017
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28. MicroRNA-346 facilitates cell growth and metastasis, and suppresses cell apoptosis in human non-small cell lung cancer by regulation of XPC/ERK/Snail/E-cadherin pathway
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Dejia Li, Zhan-Peng Yuan, Shu-Jun Li, and Cheng-Cao Sun
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0301 basic medicine ,Oncology ,Aging ,Lung Neoplasms ,Carcinogenesis ,non-small cell lung cancer (NSCLC) ,Apoptosis ,medicine.disease_cause ,Metastasis ,Mice ,chemistry.chemical_compound ,0302 clinical medicine ,Carcinoma, Non-Small-Cell Lung ,Neoplasm Metastasis ,Extracellular Signal-Regulated MAP Kinases ,3' Untranslated Regions ,microRNA-346 (miR-346) ,Cadherins ,3. Good health ,DNA-Binding Proteins ,Gene Expression Regulation, Neoplastic ,030220 oncology & carcinogenesis ,RNA Interference ,Research Paper ,Signal Transduction ,medicine.medical_specialty ,XPC ,Biology ,03 medical and health sciences ,oncogenesis ,Cell Line, Tumor ,Internal medicine ,microRNA ,medicine ,Animals ,Humans ,Gene silencing ,Antagomir ,Cell Proliferation ,Cell growth ,Cell Biology ,medicine.disease ,MicroRNAs ,030104 developmental biology ,chemistry ,Cancer research ,Snail Family Transcription Factors ,DNA Damage ,Nucleotide excision repair - Abstract
Determinants of growth and metastasis in cancer remain of great interest to define. MicroRNAs (miRNAs) have frequently emerged as tumor metastatic regulator by acting on multiple signaling pathways. Here we report the definition of miR-346 as a novel oncogenic microRNA that facilitates non-small cell lung cancer (NSCLC) cell growth and metastasis. XPC, an important DNA damage recognition factor in nucleotide excision repair was defined as a target for down-regulation by miR-346, functioning through direct interaction with the 3'-UTR of XPC mRNA. Blocking miR-346 by an antagomiR was sufficient to inhibit NSCLC cell growth and metastasis, an effect that could be phenol-copied by RNAi-mediated silencing of XPC. In vivo studies established that miR-346 overexpression was sufficient to promote tumor growth by A549 cells in xenografts mice, relative to control cells. Overall, our results defined miR-346 as an oncogenic miRNA in NSCLC, the levels of which contributed to tumor growth and invasive aggressiveness.
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- 2016
29. RETRACTED: Comprehensive Analysis of the Expression and Prognosis for E2Fs in Human Breast Cancer
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Feng Zhang, Qian Zhang, Zhuoyue Bi, Wei Hu, Jian Zhang, Yiyan Songyang, Zhan-Peng Yuan, Cong Liu, Bo-Tao Zhan, Qi-Qiang He, Yongyi Bi, Qun Zhou, Lin-Lin Li, Shu-Jun Li, Zhen-Long Chen, Wei-Dong Hu, Guang Li, Cheng-Cao Sun, Feng-Yun Gong, De-Jia Li, and Tao Bo
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Oncology ,medicine.medical_specialty ,Breast Neoplasms ,Kaplan-Meier Estimate ,medicine.disease_cause ,Disease-Free Survival ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Internal medicine ,Drug Discovery ,Genetics ,medicine ,Biomarkers, Tumor ,Humans ,RNA, Messenger ,Precision Medicine ,Molecular Biology ,E2F4 ,Survival analysis ,030304 developmental biology ,E2F2 ,Neoplasm Staging ,Pharmacology ,0303 health sciences ,business.industry ,Gene Expression Profiling ,Computational Biology ,medicine.disease ,Prognosis ,E2F Transcription Factors ,Retraction ,Gene expression profiling ,Gene Expression Regulation, Neoplastic ,Tumor progression ,030220 oncology & carcinogenesis ,Disease Progression ,Molecular Medicine ,Original Article ,Female ,Neoplasm Recurrence, Local ,Carcinogenesis ,business - Abstract
E2F transcription factors (E2Fs), a group of genes that encode a family of transcription factors, have been identified as being involved in the tumor progression of various cancer types. Increasing experimental evidence indicates that E2Fs are implicated in breast cancer tumorigenesis. However, the diverse expression patterns and prognostic values of eight E2Fs have yet to be analyzed. Herein we investigated the transcriptional and survival data of E2Fs in patients with breast cancer from the Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), Kaplan-Meier Plotter, and cBioPortal databases. We found that the expression levels of E2F1–3 and 5–8 were higher in breast cancer tissues than in normal breast tissues, whereas the expression level of E2F4 was lower in the former than in the latter. The expression levels of E2F2, 5, 7, and 8 were correlated with advanced tumor stage. Survival analysis using the Kaplan-Meier Plotter database revealed that the high transcription levels of E2F1–3, 5, 7, and 8 were associated with low relapse-free survival in all of the patients with breast cancer. Conversely, high E2F4 and E2F6 levels predicted high relapse-free survival in these patients. This study implied that E2F1–3, 5, 7, and 8 are potential targets of precision therapy for patients with breast cancer and that E2F4 and 6 are new biomarkers for the prognosis of breast cancer.
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- 2019
30. Long noncoding RNA XIST acts as an oncogene in non-small cell lung cancer by epigenetically repressing KLF2 expression
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Cheng-Cao Sun, Jing Fang, and Cheng Gong
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Male ,0301 basic medicine ,Lung Neoplasms ,Carcinogenesis ,Kruppel-Like Transcription Factors ,Biophysics ,non-small cell lung cancer (NSCLC) ,Apoptosis ,Biology ,medicine.disease_cause ,Biochemistry ,Epigenesis, Genetic ,03 medical and health sciences ,0302 clinical medicine ,Cell Movement ,Transcription (biology) ,Carcinoma, Non-Small-Cell Lung ,Cell Line, Tumor ,medicine ,Humans ,Gene silencing ,Enhancer of Zeste Homolog 2 Protein ,Molecular Biology ,Aged ,Cell Proliferation ,Neoplasm Staging ,Gene knockdown ,RNA ,Cell Biology ,Middle Aged ,Prognosis ,medicine.disease ,Survival Analysis ,Long non-coding RNA ,Tumor Burden ,respiratory tract diseases ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cancer research ,Female ,RNA, Long Noncoding ,XIST ,Protein Binding ,Signal Transduction - Abstract
Recently, long noncoding RNAs (lncRNAs) have been identified as critical regulators in numerous types of cancers, including non-small cell lung cancer (NSCLC). X inactivate-specific transcript (XIST) has been found to be up-regulated and acts as an oncogene in gastric cancer and hepatocellular carcinoma, but little is known about its expression pattern, biological function and underlying mechanism in NSCLC. Here, we identified XIST as an oncogenic lncRNA by driving tumorigenesis in NSCLC. We found that XIST is over-expressed in NSCLC, and its increased level is associated with shorter survival and poorer prognosis. Knockdown of XIST impaired NSCLC cells proliferation, migration and invasion in vitro, and repressed the tumorigenicity of NSCLC cells in vivo. Mechanistically, RNA immune-precipitation (RIP) and RNA pull-down experiment demonstrated that XIST could simultaneously interact with EZH2 to suppress transcription of its potential target KLF2. Additionally, rescue experiments revealed that XIST's oncogenic functions were partly depending on silencing KLF2 expression. Collectively, our findings expound how XIST over-expression endows an oncogenic function in NSCLC.
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- 2016
31. Long non-coding RNA NEAT1 promotes non-small cell lung cancer progression through regulation of miR-377-3p-E2F3 pathway
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Liang Wang, Shu-Jun Li, Cheng-Cao Sun, Feng Zhang, Yongyong Xi, Yongyi Bi, and Dejia Li
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Adult ,Male ,0301 basic medicine ,Lung Neoplasms ,long non-coding RNA NEAT1 (lncRNA NEAT1) ,Mice, Nude ,non-small cell lung cancer (NSCLC) ,Biology ,Bioinformatics ,medicine.disease_cause ,Metastasis ,Mice ,03 medical and health sciences ,0302 clinical medicine ,hsa-miRNA-377-3p (miR-377-3p) ,Carcinoma, Non-Small-Cell Lung ,Cell Line, Tumor ,microRNA ,medicine ,Animals ,Humans ,Aged ,Aged, 80 and over ,Mice, Inbred BALB C ,Oncogene ,Competing endogenous RNA ,Cancer ,Middle Aged ,medicine.disease ,Long non-coding RNA ,respiratory tract diseases ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,E2F3 ,tumorigenesis ,030104 developmental biology ,Oncology ,A549 Cells ,E2F3 Transcription Factor ,030220 oncology & carcinogenesis ,Disease Progression ,Cancer research ,Female ,RNA, Long Noncoding ,Carcinogenesis ,Signal Transduction ,Research Paper - Abstract
// Chengcao Sun 1 , Shujun Li 1, 2 , Feng Zhang 1 , Yongyong Xi 1 , Liang Wang 1 , Yongyi Bi 1 , Dejia Li 1 1 Department of Occupational and Environmental Health, School of Public Health, Wuhan University, Wuhan, P. R. China 2 Wuhan Hospital for the Prevention and Treatment of Occupational Diseases, Wuhan, P. R. China Correspondence to: Dejia Li, email: lodjlwhu@sina.com Keywords: long non-coding RNA NEAT1 (lncRNA NEAT1), hsa-miRNA-377-3p (miR-377-3p), E2F3 , non-small cell lung cancer (NSCLC), tumorigenesis Received: February 16, 2016 Accepted: May 05, 2016 Published: June 16, 2016 ABSTRACT Recently, the long non-coding RNA (lncRNA) NEAT1 has been identified as an oncogenic gene in multiple cancer types and elevated expression of NEAT1 was tightly linked to tumorigenesis and cancer progression. However, the molecular basis for this observation has not been characterized in progression of non-small cell lung cancer (NSCLC). In our studies, we identified NEAT1 was highly expressed in patients with NSCLC and was a novel regulator of NSCLC progression. Patients whose tumors had high NEAT1 expression had a shorter overall survival than patients whose tumors had low NEAT1 expression. Further, NEAT1 significantly accelerates NSCLC cell growth and metastasis in vitro and tumor growth in vivo. Additionally, by using bioinformatics study and RNA pull down combined with luciferase reporter assays, we demonstrated that NEAT1 functioned as a competing endogenous RNA (ceRNA) for hsa-miR-377-3p, antagonized its functions and led to the de-repression of its endogenous targets E2F3, which was a core oncogene in promoting NSCLC progression. Taken together, these observations imply that the NEAT1 modulated the expression of E2F3 gene by acting as a ceRNA, which may build up the missing link between the regulatory miRNA network and NSCLC progression.
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- 2016
32. Hsa-miR-134 suppresses non-small cell lung cancer (NSCLC) development through down-regulation of CCND1
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Shu-Jun Li, Cheng-Cao Sun, and Dejia Li
- Subjects
0301 basic medicine ,Male ,Lung Neoplasms ,proliferation ,Transplantation, Heterologous ,cyclin D1 ,non-small cell lung cancer (NSCLC) ,Down-Regulation ,Mice, Nude ,hsa-miRNA-134 (miR-134) ,Apoptosis ,Biology ,03 medical and health sciences ,0302 clinical medicine ,Cyclin D1 ,Cyclin D2 ,Cell Movement ,Carcinoma, Non-Small-Cell Lung ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Viability assay ,neoplasms ,Aged ,Cell Proliferation ,Mice, Inbred BALB C ,Oncogene ,Cell growth ,Cell migration ,Middle Aged ,medicine.disease ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,030104 developmental biology ,Oncology ,A549 Cells ,030220 oncology & carcinogenesis ,Immunology ,Cancer research ,Female ,Research Paper - Abstract
// Cheng-Cao Sun 1 , Shu-Jun Li 1, 2 , De-Jia Li 1 1 Department of Occupational and Environmental Health, School of Public Health, Wuhan University, Wuhan, P. R. China 2 Wuhan Hospital for The Prevention and Treatment of Occupational Diseases, Wuhan, P. R. China Correspondence to: De-Jia Li, email: lodjlwhu@sina.com Keywords: hsa-miRNA-134 (miR-134), cyclin D1, non-small cell lung cancer (NSCLC), proliferation, apoptosis Received: November 29, 2015 Accepted: April 18, 2016 Published: June 14, 2016 ABSTRACT Hsa-miRNA-134 (miR-134) has recently been discovered to have anticancer efficacy in different organs. However, the role of miR-134 on non-small cell lung cancer (NSCLC) is still ambiguous. In this study, we investigated the role of miR-134 on the development of NSCLC. The results indicated that miR-134 was significantly down-regulated in primary tumor tissues and very low levels were found in NSCLC cell lines. Ectopic expression of miR-134 in NSCLC cell lines significantly suppressed cell growth as evidenced by cell viability assay, colony formation assay and BrdU staining, through inhibition of cyclin D1, cyclin D2, CDK4 and up-regulation of p57(Kip2) and p21(Waf1/Cip1). In addition, miR-134 induced apoptosis, as indicated by concomitantly with up-regulation of key apoptosis protein cleaved caspase-3, and down-regulation of anti-apoptosis protein Bcl2. Moreover, miR-134 inhibited cellular migration and invasiveness through inhibition of matrix metalloproteinases (MMP)-7 and MMP-9. Further, oncogene CCND1 was revealed to be a putative target of miR-134, which was inversely correlated with miR-134 expression in NSCLC. Taken together, our results demonstrated that miR-134 played a pivotal role on NSCLC through inhibiting cell proliferation, migration, invasion, and promoting apoptosis by targeting oncogenic CCND1 .
- Published
- 2016
33. Integrative analysis of microRNA and mRNA expression profiles in non-small-cell lung cancer
- Author
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Song-Ping Xie, Cheng-Cao Sun, Chao Yang, Jian Huang, Dejia Li, and X Liang
- Subjects
0301 basic medicine ,Cancer Research ,Small RNA ,Lung Neoplasms ,Biology ,Transcriptome ,03 medical and health sciences ,Carcinoma, Non-Small-Cell Lung ,microRNA ,Cluster Analysis ,Humans ,Gene silencing ,RNA, Messenger ,Molecular Biology ,Gene ,Regulation of gene expression ,Gene Expression Profiling ,Computational Biology ,High-Throughput Nucleotide Sequencing ,RNA ,Molecular biology ,Gene Expression Regulation, Neoplastic ,Gene expression profiling ,MicroRNAs ,030104 developmental biology ,Cancer research ,Molecular Medicine - Abstract
Non-small-cell lung cancer (NSCLC) represents the most common deadly disease. Emerging evidences suggest that abnormal epigenetic modulation via mRNAs and microRNAs (miRNAs) might be involved in the tumorigenesis. To explore novel therapeutic target of NSCLC, a more detailed mRNAs and miRNA expression profiling study is needed. High-quality total RNA including miRNA was isolated from NSCLC tissue and para-carcinoma tissue and used for RNA and small RNA sequencing. Results were analyzed bioinformatically and validated using quantitative real-time (qRT)-PCR. A total of 3530 genes (1977 up-regulated and 1553 down-regulated) and 211 miRNAs (171 up-regulated and 30 down-regulated) were differentially expressed (DE) in NSCLC tissue versus adjacent normal tissues. Furthermore, 157 novel miRNAs were predicted in our samples. Of these, 918 significant miRNA-mRNA pairs were identified, consisting of 100 miRNAs and 443 mRNAs. Gene ontology analysis revealed that most of the target genes were enriched in the terms of plasma membrane, binding, and multiple biological-molecular signaling processes. Pathway analysis of these miRNA signatures highlights their critical roles in calcium signaling pathway. Using qRT-PCR, the expression of several DE genes (KRAS and RBM5) and miRNAs (miR-1-5p, let-7b-5p, miR-21-5p, miR-1290, miR-149-5p, chr8_28846, chrX_31594, and chr9_29897) were confirmed. The integrative analysis based on mRNA and miRNA profiling may provide more potential molecular for the tumorigenesis and development of NSCLC.
- Published
- 2016
34. Hsa-miR-329 exerts tumor suppressor function through down-regulation of MET in non-small cell lung cancer
- Author
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Yongyong Xi, Feng Zhang, Cuili Yang, Dejia Li, Cheng-Cao Sun, Liang Wang, Jing-Yu Pan, and Shu-Jun Li
- Subjects
Male ,0301 basic medicine ,Lung Neoplasms ,proliferation ,Transplantation, Heterologous ,Down-Regulation ,Mice, Nude ,non-small cell lung cancer (NSCLC) ,Apoptosis ,Biology ,03 medical and health sciences ,Cyclin D1 ,Cyclin D2 ,Cell Movement ,Carcinoma, Non-Small-Cell Lung ,Cell Line, Tumor ,microRNA ,medicine ,Animals ,Humans ,Genes, Tumor Suppressor ,Viability assay ,Lung cancer ,3' Untranslated Regions ,Aged ,Cell Proliferation ,Mice, Inbred BALB C ,Oncogene ,Cell growth ,Middle Aged ,Proto-Oncogene Proteins c-met ,medicine.disease ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,030104 developmental biology ,Oncology ,A549 Cells ,Immunology ,MET ,Cancer research ,RNA Interference ,hsa-miRNA-329(miR-329) ,Research Paper - Abstract
MicroRNAs (miRNAs) act as key regulators of multiple cancers. Hsa-miR-329 (miR-329) functions as a tumor suppressor in some malignancies. However, its role on lung cancer remains poorly understood. In this study, we investigated the role of miR-329 on the development of lung cancer. The results indicated that miR-329 was decreased in primary lung cancer tissues compared with matched adjacent normal lung tissues and very low levels were found in a non-small cell lung cancer (NSCLC) cell lines. Ectopic expression of miR-329 in lung cancer cell lines substantially repressed cell growth as evidenced by cell viability assay, colony formation assay and BrdU staining, through inhibiting cyclin D1, cyclin D2 and up-regulatiing p57(Kip2) and p21(WAF1/CIP1). In addition, miR-329 promoted NSCLC cell apoptosis, as indicated by up-regulation of key apoptosis gene cleaved caspase-3, and down-regulation of anti-apoptosis gene Bcl2. Moreover, miR-329 inhibited cellular migration and invasiveness through inhibiting matrix metalloproteinases (MMP)-7 and MMP-9. Further, oncogene MET was revealed to be a putative target of miR-329, which was inversely correlated with miR-329 expression. Furthermore, down-regulation of MET by siRNA performed similar effects to over-expression of miR-329. Collectively, our results demonstrated that miR-329 played a pivotal role in lung cancer through inhibiting cell proliferation, migration, invasion, and promoting apoptosis by targeting oncogenic MET.
- Published
- 2016
35. Hsa-miR-326 targets CCND1 and inhibits non-small cell lung cancer development
- Author
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Cheng-Cao Sun, Yunfeng Fu, Feng Zhang, Liang Wang, Yongyong Xi, Chuan-Feng Huang, Cuili Yang, Shu-Jun Li, and Dejia Li
- Subjects
0301 basic medicine ,Lung Neoplasms ,cyclin D1 ,Fluorescent Antibody Technique ,non-small cell lung cancer (NSCLC) ,Apoptosis ,Immunoenzyme Techniques ,Mice ,0302 clinical medicine ,Cell Movement ,Carcinoma, Non-Small-Cell Lung ,Tumor Cells, Cultured ,Medicine ,Mice, Inbred BALB C ,Reverse Transcriptase Polymerase Chain Reaction ,Prognosis ,Gene Expression Regulation, Neoplastic ,Survival Rate ,Oncology ,030220 oncology & carcinogenesis ,Research Paper ,proliferation ,Blotting, Western ,Mice, Nude ,Real-Time Polymerase Chain Reaction ,03 medical and health sciences ,Cyclin D1 ,Cyclin D2 ,microRNA ,Animals ,Humans ,RNA, Messenger ,Viability assay ,Lung cancer ,neoplasms ,Cell Proliferation ,Neoplasm Staging ,Oncogene ,business.industry ,Cell growth ,medicine.disease ,Xenograft Model Antitumor Assays ,MicroRNAs ,030104 developmental biology ,Immunology ,Cancer research ,business ,Hsa-miRNA-326 (miR-326) ,Follow-Up Studies - Abstract
// Chengcao Sun 1, * , Chuanfeng Huang 1, 2, * , Shujun Li 1, 3 , Cuili Yang 1 , Yongyong Xi 1 , Liang Wang 1 , Feng Zhang 1 , Yunfeng Fu 4 , Dejia Li 1 1 Department of Occupational and Environmental Health, School of Public Health, Wuhan University, 430071 Wuhan, P.R.China 2 Department of Pharmacology, Basic Medical School, Nanyang Medical College, 473003 Nanyang, P.R.China 3 Wuhan Hospital for the Prevention and Treatment of Occupational Diseases, 430071 Wuhan, P.R.China 4 The Third Xiang-Ya Hospital, Central South University, 410013 Changsha, P.R.China * These authors contributed equally to this work Correspondence to: Dejia Li, e-mail: lodjlwhu@sina.com Yunfeng Fu, e-mail: fuyfeng427@163.com Keywords: Hsa-miRNA-326 (miR-326), cyclin D1, non-small cell lung cancer (NSCLC), proliferation, apoptosis Received: August 18, 2015 Accepted: January 13, 2016 Published: January 29, 2016 ABSTRACT Hsa-miRNA-326 (miR-326) has recently been discovered having anticancer efficacy in different organs. However, the role of miR-326 on non-small cell lung cancer (NSCLC) is still ambiguous. In this study, we investigated the role of miR-326 on the development of NSCLC. The results indicated that miR-326 was significantly down-regulated in primary tumor tissues and very low levels were found in NSCLC cell lines. Ectopic expression of miR-326 in NSCLC cell lines significantly suppressed cell growth as evidenced by cell viability assay, colony formation assay and BrdU staining, through inhibition of cyclin D1, cyclin D2, CDK4 and up-regulation of p57(Kip2) and p21(Waf1/Cip1). In addition, miR-326 induced apoptosis, as indicated by concomitantly with up-regulation of key apoptosis protein cleaved caspase-3, and down-regulation of anti-apoptosis protein Bcl2. Moreover, miR-326 inhibited cellular migration and invasiveness through inhibition of matrix metalloproteinases (MMP)-7 and MMP-9. Further, oncogene CCND1 was revealed to be a putative target of miR-326, which was inversely correlated with miR-326 expression in NSCLC. Taken together, our results demonstrated that miR-326 played a pivotal role on NSCLC through inhibiting cell proliferation, migration, invasion, and promoting apoptosis by targeting oncogenic CCND1 .
- Published
- 2016
36. Hsa-miR-139-5p inhibits proliferation and causes apoptosis associated with down-regulation of c-Met
- Author
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Feng Zhang, Shu-Jun Li, Cheng-Cao Sun, Yongyi Bi, Yunfeng Fu, Cuili Yang, Xiaodong Sun, Liang Wang, Yongyong Xi, Ming Sang, and Dejia Li
- Subjects
Lung Neoplasms ,C-Met ,proliferation ,Blotting, Western ,Down-Regulation ,Mice, Nude ,non-small cell lung cancer (NSCLC) ,Apoptosis ,Metastasis ,chemistry.chemical_compound ,Cyclin D1 ,Carcinoma, Non-Small-Cell Lung ,Cell Line, Tumor ,microRNA ,medicine ,Animals ,Humans ,Lung cancer ,Cell Proliferation ,c-Met ,Mice, Inbred BALB C ,Oncogene ,Reverse Transcriptase Polymerase Chain Reaction ,Cell growth ,business.industry ,Proto-Oncogene Proteins c-met ,medicine.disease ,Survival Analysis ,Xenograft Model Antitumor Assays ,Tumor Burden ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,Microscopy, Fluorescence ,Oncology ,chemistry ,Immunology ,Cancer research ,RNA Interference ,business ,Hsa-miRNA-139-5p (miR-139-5p) ,Research Paper - Abstract
Hsa-miRNA-139-5p (miR-139-5p) has recently been discovered having anticancer efficacy in different organs. However, the role of miR-139-5p on lung cancer is still ambiguous. In this study, we investigated the role of miR-139-5p on development of lung cancer. Results indicated miR-139-5p was significantly down-regulated in primary tumor tissues and very low levels were found in a non-small cell lung cancer (NSCLC) cell lines. Ectopic expression of miR-139-5p in NSCLC cell lines significantly suppressed cell growth through inhibition of cyclin D1 and up-regulation of p57(Kip2). In addition, miR-139-5p induced apoptosis, as indicated by up-regulation of key apoptosis gene cleaved caspase-3, and down-regulation of anti-apoptosis gene Bcl2. Moreover, miR-139-5p inhibited cellular metastasis through inhibition of matrix metalloproteinases (MMP)-7 and MMP-9. Further, oncogene c-Met was revealed to be a putative target of miR-139-5p, which was inversely correlated with miR-139-5p expression. Taken together, our results demonstrated that miR-139-5p plays a pivotal role in lung cancer through inhibiting cell proliferation, metastasis, and promoting apoptosis by targeting oncogenic c-Met.
- Published
- 2015
37. Transcriptional E2F1/2/5/8 as potential targets and transcriptional E2F3/6/7 as new biomarkers for the prognosis of human lung carcinoma
- Author
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Tao Bo, Zhan-Peng Yuan, Feng-Yun Gong, Zhen-Long Chen, Shu-Jun Li, Guang Li, De-Jia Li, Feng Zhang, Zhuoyue Bi, Qi-Zhu Tang, Cheng-Cao Sun, Yongyi Bi, Bo-Tao Zhan, Wei Hu, Qun Zhou, Wei-Dong Hu, and Qian Zhang
- Subjects
0301 basic medicine ,Aging ,Lung Neoplasms ,Kaplan-Meier Estimate ,Biology ,medicine.disease_cause ,03 medical and health sciences ,0302 clinical medicine ,E2F translational factors ,Carcinoma, Non-Small-Cell Lung ,Kaplan-Meier plot ,medicine ,Biomarkers, Tumor ,E2F1 ,Humans ,Lung cancer ,E2F ,E2F4 ,Survival analysis ,E2F2 ,Cell Biology ,medicine.disease ,Small Cell Lung Carcinoma ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cancer research ,Adenocarcinoma ,prognosis ,Carcinogenesis ,lung carcinoma ,Transcription Factors ,Research Paper - Abstract
E2F is a group of genes that encode a family of transcription factors (TFs) in higher eukaryotes and participate in cell cycle regulation and DNA synthesis in mammalian cells. Evidence from cell lines, mouse models, and human tissues indicates that TFs are implicated in lung cancer (LC) tumorigenesis. However, the diverse expression patterns and prognostic values of eight E2Fs have yet to be elucidated. In the current study, we examined the transcriptional and survival data of E2Fs in patients with LC from ONCOMINE, GEPIA, Kaplan-Meier Plotter, and cBioPortal databases. We found that the expression levels of E2F1/2/3/5/6/7/8 were higher in lung adenocarcinoma and squamous cell lung carcinoma tissues than in lung tissues, whereas the expression level of E2F4 was lower in the former than in the latter. The expression levels of E2F2/4/5/7/8 were correlated with advanced tumor stage. Survival analysis using the Kaplan-Meier Plotter database revealed that the high transcription levels of E2F1/2/4/5/7/8 were associated with low relapse-free survival (RFS) in all of the patients with LC. Conversely, high E2F3/6 levels predicted high RFS in these patients. This study implied that E2F3/6/7 are potential targets of precision therapy for patients with LC and that E2F1/2/4/5/8 are new biomarkers for the prognosis of LC.
- Published
- 2018
38. Editorial: Towards MiRNA Based Therapeutics for Lung Cancer
- Author
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Cheng-Cao Sun and De-Jia Li
- Subjects
0301 basic medicine ,Pharmacology ,Lung Neoplasms ,business.industry ,Antineoplastic Agents ,medicine.disease ,03 medical and health sciences ,030104 developmental biology ,Drug Resistance, Neoplasm ,Carcinoma, Non-Small-Cell Lung ,Drug Discovery ,microRNA ,Cancer research ,Medicine ,Animals ,Humans ,business ,Lung cancer - Published
- 2018
39. Long non coding RNA XIST as a prognostic cancer marker - A meta-analysis
- Author
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Cong Liu, Yiyan Songyang, Dejia Li, Wei Hu, Cheng-Cao Sun, Qun Zhou, Feng Zhang, Li Lin-lin, and Wei Zhu
- Subjects
0301 basic medicine ,Oncology ,medicine.medical_specialty ,Clinical Biochemistry ,Biochemistry ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Statistical significance ,Neoplasms ,medicine ,Biomarkers, Tumor ,Humans ,Stage (cooking) ,Pathological ,business.industry ,Biochemistry (medical) ,Cancer ,General Medicine ,medicine.disease ,Prognosis ,Long non-coding RNA ,030104 developmental biology ,Sample size determination ,030220 oncology & carcinogenesis ,Meta-analysis ,XIST ,RNA, Long Noncoding ,business - Abstract
Background The X inactivate-specific transcript (XIST), derived from XIST gene, is aberrantly expressed in various cancers. High-expression of XIST is related to poor clinical outcome. This meta-analysis evaluated the potential role of XIST as novel predictor of prognosis in human cancer. Materials and methods This meta-analysis collected eligible studies about XIST and tumor prognosis through retrieving keywords in Web of Science, PubMed, Embase and the CNKI database, from 1993 to August 21, 2017. The quantitative meta-analysis was carried out with Stata SE12.0 and RevMan3.23 software. The aim was to determine whether XIST expression is associated with cancer prognosis and clinicopathology. Results A total of 858 patients from 10 eligible studies were included in the final meta-analysis. Overall, a significant negative association between XIST and overall survival (OS) time (HR = 2.62, 95% CI: 2.18–3.14) was observed. Statistical significance was also showed in subgroup meta-analysis stratified by the country, sample size, follow-up and publication year. It was reported that increased XIST was positively related to advanced clinical TNM stage (OR = 4.03, 95% CI: 2.22–7.30), lymph node metastasis (LNM) (OR = 2.70, 95% CI: 1.73–4.21), distant metastasis (DM) (OR = 2.61, 95% CI: 1.57–4.33) and tumor size (OR = 3.10, 95% CI: 2.24–4.30). Conclusions LncRNA XIST may serve as a potential biomarker to predict solid tumor prognosis. This molecule can be effectively used to predict the clinical and pathological features of cancers.
- Published
- 2018
40. Emerging landscape of circular RNAs in lung cancer
- Author
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Qian Zhang, Wei Zhu, De-Jia Li, Yongyi Bi, Cheng-Cao Sun, Cong Liu, Yang-Yi-Yan Song, Lin-Lin Li, Feng Zhang, Qun Zhou, Zhen-Long Chen, Wei Hu, Zhuoyue Bi, and Bo-Tao Zhan
- Subjects
0301 basic medicine ,Cancer Research ,Lung Neoplasms ,RNA, Untranslated ,Treatment of lung cancer ,Computational biology ,Disease ,Biology ,03 medical and health sciences ,Circular RNA ,medicine ,RNA Precursors ,Malignant cells ,Humans ,Lung cancer ,Models, Genetic ,RNA ,Cancer ,High-Throughput Nucleotide Sequencing ,Exons ,RNA, Circular ,respiratory system ,medicine.disease ,Biomarker (cell) ,Alternative Splicing ,MicroRNAs ,030104 developmental biology ,Oncology - Abstract
Lung cancer, the leading cause of cancer deaths worldwide, is characterized with malignant cell growth. Advances in next-generation sequencing has helped us further understand RNA and identify novel circular RNAs (circRNAs) that may be useful in the early diagnosis and treatment of lung cancer. Similar to other noncoding RNAs, circRNAs present diverse biological functions in normal and disease states, including various types of cancers. This review focuses mainly on the poorly understood functions of circRNA in lung cancer. This paper also summarizes the recent advances in circRNA biogenesis, analyzes the role of circRNAs in cancers, and discusses the potential mechanisms of circRNAs in lung cancer.
- Published
- 2017
41. Down-regulation of c-Met and Bcl2 by microRNA-206, activates apoptosis, and inhibits tumor cell proliferation, migration and colony formation
- Author
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Qi-qiang He, Wen-Yang Jiang, Yongyong Xi, Dejia Li, Cheng-Cao Sun, Cuili Yang, Zhidong Liu, Ruilin Xue, Shu-Jun Li, Jie Huang, Liang Wang, Song-Ping Xie, and Suqing Wang
- Subjects
Male ,Bcl2 ,Lung Neoplasms ,Time Factors ,C-Met ,proliferation ,Mice, Nude ,Apoptosis ,Biology ,Transfection ,chemistry.chemical_compound ,Cell Movement ,Carcinoma, Non-Small-Cell Lung ,Cell Line, Tumor ,hsa-miRNA-206(miR-206) ,microRNA ,medicine ,Animals ,Humans ,Neoplasm Invasiveness ,Lung cancer ,3' Untranslated Regions ,Cell Proliferation ,c-Met ,Mice, Inbred BALB C ,non-small cell lung cancer (NSCLS) ,Binding Sites ,Cell growth ,Proto-Oncogene Proteins c-met ,medicine.disease ,Molecular biology ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,Proto-Oncogene Proteins c-bcl-2 ,Oncology ,chemistry ,Cell culture ,RNA Interference ,Signal transduction ,Protein Binding ,Signal Transduction ,Research Paper - Abstract
Hsa-miRNA-206 (miR-206), highly expressed in skeletal muscle, has recently been discovered to have anticancer properties in different tissues. However, the role of miR-206 on lung cancer is still ambiguous. In this study, we investigated the role of miR-206 on the development of lung cancer. The results indicated that miR-206 expression was suppressed in lung cancer tissues and very low levels were found in non-small cell lung cancer (NSCLS) cell liness. Transient transfection of miR-206 into cultured A549 and SK-MES-1 cells led to significant decrease in cell growth, migration, invasion and colony formation, and promoted cell apoptosis. Using bioinformatics, we identified putative miR-206 binding sites within the 3′-untranslated region (3′-UTR) of the human c-Met and Bcl2 mRNA. The expression of c-Met and Bcl2 proteins were shown to be down-regulated after treated with miR-206 by subsequent Western blot and qRT-PCR analysis. Conversely, up-regulation of c-Met and Bcl2 were confirmed in tissue samples of human lung cancer, with its level inversely correlated with miR-206 expression. In addition, miR-206 also decreased the gene expression of MMP-9, CCND1 and CCND2 while increased the gene expression of p57 (Kip2) in A549 and SK-MES-1 cells. Taken together, our results demonstrated that miR-206 suppressed c-Met and Bcl2 expression in NSCLS and could function as a potent tumor suppressor in c-Met/Bcl2-over expressing tumors. Inhibition of miR-206 function could contribute to aberrant cell proliferation, migration, invasion and apoptosis, leading to NSCLS development.
- Published
- 2015
42. Sulforaphane Attenuates Muscle Inflammation in Dystrophin-deficient mdx Mice via NF-E2-related Factor 2 (Nrf2)-mediated Inhibition of NF-κB Signaling Pathway
- Author
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Cuili Yang, Ruilin Xue, Cheng-Cao Sun, Yongyong Xi, Liang Wang, Qian-Long Zhao, Shu-Jun Li, and Dejia Li
- Subjects
Male ,medicine.medical_specialty ,NF-E2-Related Factor 2 ,medicine.medical_treatment ,Duchenne muscular dystrophy ,Anti-Inflammatory Agents ,Inflammation ,Biology ,medicine.disease_cause ,digestive system ,environment and public health ,Biochemistry ,Antioxidants ,Proinflammatory cytokine ,Dystrophin ,Mice ,chemistry.chemical_compound ,Isothiocyanates ,Internal medicine ,medicine ,Animals ,Muscle, Skeletal ,Molecular Biology ,NF-kappa B ,Membrane Proteins ,Molecular Bases of Disease ,NF-κB ,Cell Biology ,respiratory system ,medicine.disease ,Mice, Inbred C57BL ,Muscular Dystrophy, Duchenne ,Oxidative Stress ,Cytokine ,Endocrinology ,chemistry ,Sulfoxides ,Immunology ,Mice, Inbred mdx ,biology.protein ,Tumor necrosis factor alpha ,medicine.symptom ,Gene Deletion ,Heme Oxygenase-1 ,Oxidative stress ,Signal Transduction - Abstract
Inflammation is widely distributed in patients with Duchenne muscular dystrophy and ultimately leads to progressive deterioration of muscle function with chronic muscle damage, oxidative stress, and reduced oxidative capacity. NF-E2-related factor 2 (Nrf2) plays a critical role in defending against inflammation in different tissues via activation of phase II enzyme heme oxygenase-1 and inhibition of the NF-κB signaling pathway. However, the role of Nrf2 in the inflammation of dystrophic muscle remains unknown. To determine whether Nrf2 may counteract inflammation in dystrophic muscle, we treated 4-week-old male mdx mice with the Nrf2 activator sulforaphane (SFN) by gavage (2 mg/kg of body weight/day) for 4 weeks. The experimental results demonstrated that SFN treatment increased the expression of muscle phase II enzyme heme oxygenase-1 in an Nrf2-dependent manner. Inflammation in mice was reduced by SFN treatment as indicated by decreased infiltration of immune cells and expression of the inflammatory cytokine CD45 and proinflammatory cytokines tumor necrosis factor-α, interleukin-1β, and interleukin-6 in the skeletal muscles of mdx mice. In addition, SFN treatment also decreased the expression of NF-κB(p65) and phosphorylated IκB kinase-α as well as increased inhibitor of κB-α expression in mdx mice in an Nrf2-dependent manner. Collectively, these results show that SFN-induced Nrf2 can alleviate muscle inflammation in mdx mice by inhibiting the NF-κB signaling pathway.
- Published
- 2015
43. Sulforaphane alleviates muscular dystrophy inmdxmice by activation of Nrf2
- Author
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Ruilin Xue, Cheng-Cao Sun, Lei Pan, Dejia Li, Xuejiao Ma, Liang Wang, Cuili Yang, Shu-Jun Li, and Ting Zhang
- Subjects
Male ,medicine.medical_specialty ,NF-E2-Related Factor 2 ,Physiology ,Duchenne muscular dystrophy ,Drug Evaluation, Preclinical ,medicine.disease_cause ,Muscle hypertrophy ,Random Allocation ,chemistry.chemical_compound ,Sarcolemma ,Isothiocyanates ,Physiology (medical) ,Internal medicine ,Lactate dehydrogenase ,NAD(P)H Dehydrogenase (Quinone) ,medicine ,Animals ,Anticarcinogenic Agents ,Muscular dystrophy ,Muscle, Skeletal ,Inflammation ,biology ,Membrane Proteins ,Heart ,Muscular Dystrophy, Animal ,medicine.disease ,Antioxidant Response Elements ,Mice, Inbred C57BL ,Oxidative Stress ,Endocrinology ,Gene Expression Regulation ,Biochemistry ,chemistry ,Sulfoxides ,biology.protein ,Creatine kinase ,Heme Oxygenase-1 ,Oxidative stress ,Signal Transduction - Abstract
Sulforaphane (SFN), one of the most important isothiocyanates in the human diet, is known to have chemo-preventive and antioxidant activities in different tissues via activation of nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated induction of antioxidant/phase II enzymes, such as heme oxygenase-1 and NAD(P)H quinone oxidoreductase 1. However, its effects on muscular dystrophy remain unknown. This work was undertaken to evaluate the effects of SFN on Duchenne muscular dystrophy. Four-week-old mdx mice were treated with SFN by gavage (2 mg·kg body wt−1·day−1for 8 wk), and our results demonstrated that SFN treatment increased the expression and activity of muscle phase II enzymes NAD(P)H quinone oxidoreductase 1 and heme oxygenase-1 with a Nrf2-dependent manner. SFN significantly increased skeletal muscle mass, muscle force (∼30%), running distance (∼20%), and GSH-to-GSSG ratio (∼3.2-fold) of mdx mice and decreased the activities of plasma creatine phosphokinase (∼45%) and lactate dehydrogenase (∼40%), gastrocnemius hypertrophy (∼25%), myocardial hypertrophy (∼20%), and malondialdehyde levels (∼60%). Furthermore, SFN treatment also reduced the central nucleation (∼40%), fiber size variability, and inflammation and improved the sarcolemmal integrity of mdx mice. Collectively, these results show that SFN can improve muscle function and pathology and protect dystrophic muscle from oxidative damage in mdx mice associated with Nrf2 signaling pathway, which indicate Nrf2 may have clinical implications for the treatment of patients with muscular dystrophy.
- Published
- 2015
44. MicroRNAs: A novel potential biomarker for diagnosis and therapy in patients with non-small cell lung cancer
- Author
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Yongyong Xi, Xin Wang, Qun Zhou, Qi-qiang He, Cheng-Cao Sun, Shao-Xin Huang, Dejia Li, Cong Liu, Liang Wang, Feng Zhang, and Shu-Jun Li
- Subjects
0301 basic medicine ,Lung Neoplasms ,Review Article ,Bioinformatics ,Exosomes ,03 medical and health sciences ,0302 clinical medicine ,Carcinoma, Non-Small-Cell Lung ,microRNA ,medicine ,Carcinoma ,Biomarkers, Tumor ,Animals ,Humans ,In patient ,Lung cancer ,Regulation of gene expression ,business.industry ,Gene Expression Profiling ,Cell Biology ,General Medicine ,medicine.disease ,Microvesicles ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,030104 developmental biology ,030220 oncology & carcinogenesis ,Potential biomarkers ,Non small cell ,business - Abstract
Background Lung cancer is still one of the most serious causes of cancer-related deaths all over the world. MicroRNAs (miRNAs) are defined as small non-coding RNAs which could play a pivotal role in post-transcriptional regulation of gene expression. Increasing evidence demonstrated dysregulation of miRNA expression associates with the development and progression of NSCLC. Aims To emphasize a variety of tissue-specific miRNAs, circulating miRNAs and miRNA-derived exosomes could be used as potential diagnostic and therapeutic biomarkers in NSCLC patients. Materials & Methods In the current review, we paid attention to the significant discoveries of preclinical and clinical studies, which performed on tissue-specific miRNA, circulating miRNA and exosomal miRNA. The related studies were obtained through a systematic search of Pubmed, Web of Science, Embase. Results A variety of tissue-specific miRNAs and circulating miRNAs with high sensitivity and specificity which could be used as potential diagnostic and therapeutic biomarkers in NSCLC patients. In addition, we emphasize that the miRNA-derived exosomes become novel diagnostic biomarkers potentially in these patients with NSCLC. Conclusion MiRNAs have emerged as non-coding RNAs, which have potential to be candidates for the diagnosis and therapy of NSCLC.
- Published
- 2017
45. MiRNA-based Therapeutic Strategy in Lung Cancer
- Author
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Hu Wang, Cheng-Cao Sun, Guang Li, Jing Fang, and Ying Wang
- Subjects
0301 basic medicine ,Lung Neoplasms ,Antineoplastic Agents ,Drug resistance ,Treatment of lung cancer ,Tumor initiation ,03 medical and health sciences ,0302 clinical medicine ,Drug Discovery ,microRNA ,medicine ,Biomarkers, Tumor ,Animals ,Humans ,Lung cancer ,Pharmacology ,business.industry ,RNA ,medicine.disease ,MicroRNAs ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cancer research ,Adenocarcinoma ,Human genome ,business - Abstract
Lung cancer is one of the most common malignant tumors in the world. Although advanced therapies have been applied for the treatment of lung cancer, the prolongation of overall survival is limited due to treatment resistance. MicroRNAs (miRNAs) are a class of small non-coding, endogenous RNA molecules (about 19-23 nucleotides in length), which could regulate numerous human genes and play key roles in a variety of diseases. MiRNAs are dysregulated in lung cancer and participate in tumor initiation, development and drug resistance. Recent studies showed a new therapeutic strategy for cancer therapy based on miRNAs. In this review, we briefly summarize one classic pathway of miRNAs in lung cancer, and discuss a new miRNA-based therapeutic strategy to manage lung cancer.
- Published
- 2017
46. The novel miR-9501 inhibits cell proliferation, migration and activates apoptosis in non-small cell lung cancer
- Author
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Feng Zhang, Cheng-Cao Sun, Liang Wang, Cuili Yang, Dejia Li, and Yongyong Xi
- Subjects
0301 basic medicine ,Cancer Research ,Lung Neoplasms ,non-small cell lung cancer (NSCLC) ,Apoptosis ,Biology ,medicine.disease_cause ,Transfection ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,Cell Movement ,Carcinoma, Non-Small-Cell Lung ,Cell Line, Tumor ,microRNA ,medicine ,Humans ,Lung cancer ,Cell Proliferation ,A549 cell ,Cell growth ,Cancer ,Hematology ,General Medicine ,medicine.disease ,Cell biology ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Carcinogenesis - Abstract
Accumulating evidences suggest that lots of microRNAs (miRNAs) play crucial roles in (patho-)physiological processes of lung cancer, including metastasis, drug-resistance or tumorigenesis. They mediate the progression of cell growth, migration and invasion by regulating the expression of special genes. MiRNA expression patterns could also serve as diagnostic/prognostic biomarkers. Cancer therapies mediated by miRNAs remain tremendous potential and challenges. Our previous small RNA-seq assay found that the novel miR-9501 was down-regulated in lung cancer tissues compared with adjacent non-cancer tissues. In this study, our results verified that miR-9501 was significantly down-regulated in lung cancer tissues and its expression levels were remarkably suppressed in non-small cell lung cancer cell lines. Then, we characterized and investigated the novel miR-9501 in A549 cells. Transient transfection of miR-9501 into cultured A549 cells led to remarkable decrease in cell proliferation, migration and increase apoptosis. These data demonstrated that miR-9501 might be a tumor suppressor for lung cancer therapy.
- Published
- 2016
47. The role of miR-139-5p and miR-206 in non-small cell lung cancer (NSCLC) by targeting c-Met
- Author
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Cheng-Cao Sun, Dejia Li, and Shu-Jun Li
- Subjects
Oncology ,A549 cell ,medicine.medical_specialty ,C-Met ,Cell growth ,non-small cell lung cancer (NSCLC) ,General Medicine ,Biology ,medicine.disease ,Metastasis ,chemistry.chemical_compound ,chemistry ,Apoptosis ,Internal medicine ,microRNA ,Cancer research ,medicine ,Lung cancer - Abstract
Increasing evidences have confirmed that ectopic miRNAs are key regulatory factors in various types of cancers. Both hsa-miRNA-206 (miR-206) and hsa-miRNA-139-5p (miR-139-5p) have been demonstrated that possess anticancer properties in a variety of tissues and organs. In our recent investigations, we discovered miR-139-5p and miR-206 played a crucial role in lung cancer progression. There were extremely low levels of miR-206 and miR-139-5p in NSCLC (non-small cell lung cancer) cell lines as well as expression of them were inhibited in lung cancer tissues, respectively. Moreover, we found that miR-206 through targeting 3′-UTR(3'-untranslated region )of Bcl-2 and c-Met mRNA that promoted cell apoptosis as well as suppressed non-small cell lung cancer SK-MES-1 and A549 cells colony formation, growth, invasion and metastasis. The analogical phenomenon was also discovered in miR-139-5p that targeted tumorigenic c-Met, which contributed to promotion of apoptosis and inhibition of cell proliferation and migration in non-small cell lung cancer.
- Published
- 2016
48. MicroRNA-187-3p mitigates non-small cell lung cancer (NSCLC) development through down-regulation of BCL6
- Author
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Yongyong Xi, Liang Wang, Shu-Jun Li, Cheng-Cao Sun, Dejia Li, Cuili Yang, and Feng Zhang
- Subjects
0301 basic medicine ,Lung Neoplasms ,Cell Survival ,Biophysics ,non-small cell lung cancer (NSCLC) ,Down-Regulation ,Biology ,Biochemistry ,03 medical and health sciences ,Carcinoma, Non-Small-Cell Lung ,Cell Line, Tumor ,microRNA ,medicine ,Humans ,Neoplasm Invasiveness ,Viability assay ,Molecular Biology ,Cell Proliferation ,Oncogene ,Cell growth ,Cell migration ,Cell Biology ,medicine.disease ,respiratory tract diseases ,DNA-Binding Proteins ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,030104 developmental biology ,Apoptosis ,Cancer research ,Proto-Oncogene Proteins c-bcl-6 ,Ectopic expression - Abstract
Hsa-microRNA-187-3p (miR-187-3p) has recently been discovered having anticancer efficacy in different organs. However, the role of miR-187-3p on non-small cell lung cancer (NSCLC) is still ambiguous. In this study, we investigated the role of miR-187-3p on the development of NSCLC. The results indicated that miR-187-3p was significantly down-regulated in primary tumor tissues and very low levels were found in NSCLC cell lines. Ectopic expression of miR-187-3p in NSCLC cell lines significantly suppressed cell growth as evidenced by cell viability assay and colony formation assay, through inhibition of BCL6. In addition, miR-187-3p induced apoptosis, as indicated by concomitantly with up-regulation of the activities of caspase-3 and caspase-7, and inhibited cellular migration and invasiveness through inhibition of BCL6. Further, oncogene BCL6 was revealed to be a putative target of miR-187-3p, which was inversely correlated with miR-187-3p expression in NSCLC. Taken together, our results demonstrated that miR-187-3p played a pivotal role on NSCLC through inhibiting cell proliferation, migration, invasion, and promoting apoptosis by targeting oncogenic BCL6.
- Published
- 2016
49. Role of miR-10b in non-small cell lung cancer (NSCLC) cells by targeting Klotho
- Author
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Junchao Huang, Dejia Li, Cheng-Cao Sun, Shu-Jun Li, and Jing-Yu Pan
- Subjects
Oncology ,medicine.medical_specialty ,business.industry ,Cell ,non-small cell lung cancer (NSCLC) ,General Medicine ,Prognosis Marker ,medicine.disease ,respiratory tract diseases ,medicine.anatomical_structure ,Apoptosis ,Internal medicine ,Carcinoma ,Medicine ,Gene silencing ,business ,Enhancer ,Klotho - Abstract
MiR-10b was overexpressed in various cancers, including NSCLC. In early study, miR-10b was described as a carcinoma enhancer in NSCLC. Our recent study showed that silencing of miR-10b could promote NSCLC cells apoptosis and decrease proliferation, and regulation of these cell behaviors might target Klotho via miR-10b. In addition, we also explored the correlation between miR-10b and Klotho or other underlying targets. Our investigation indicated that miR-10b could play a critical role as a helpful prognosis marker and underlying target in terms of therapy of NSCLC.
- Published
- 2015
50. Red Meat Consumption and the Risk of Stroke: A Dose-Response Meta-analysis of Prospective Cohort Studies
- Author
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Cheng-Cao Sun, Cuili Yang, Dejia Li, Yongyong Xi, Lei Pan, and Liang Wang
- Subjects
medicine.medical_specialty ,030204 cardiovascular system & hematology ,Recommended Dietary Allowances ,Risk Assessment ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Internal medicine ,medicine ,Humans ,030212 general & internal medicine ,Prospective Studies ,Prospective cohort study ,Stroke ,Cerebral infarction ,business.industry ,Rehabilitation ,Feeding Behavior ,medicine.disease ,Confidence interval ,Surgery ,Diet ,Meat Products ,Red Meat ,Red Meat Consumption ,Relative risk ,Red meat ,Neurology (clinical) ,Cardiology and Cardiovascular Medicine ,Risk assessment ,business - Abstract
Background Prospective studies of red meat consumption and risk of stroke have provided inconsistent results. We aimed to assess this association by conducting a meta-analysis of prospective cohort studies. Methods Relevant studies were identified by searching PubMed and EMBASE through April 1, 2013. Summary relative risks (RR) and the corresponding 95% confidence intervals (CIs) were estimated by random-effect or fixed-effect models. Results Seven prospective cohort studies were included in the analyses, involving 2,079,236 subjects and 21,730 strokes cases. Total red meat consumption was associated with total stroke (RR = 1.14, 95% CI 1.05-1.24), cerebral infarction (RR = 1.13, 95% CI 1.0-1.28), and ischemic stroke (RR = 1.22, 95% CI 1.01-1.46). A significant association was found between consumption of processed red meat and total stroke (RR = 1.17, 95% CI 1.09-1.27). Consumption of fresh red meat was significantly associated with total stroke (RR = 1.13, 95% CI 1.04-1.22) and ischemic stroke (RR = 1.15, 95% CI 1.03-1.29). However, no evidence suggests that any type of meat was associated with hemorrhagic stroke. Also, no association was found between consumption of processed red meat and ischemic stroke (RR = 1.15, 95% CI .98-1.36) and between consumption of fresh red meat and cerebral infarction (RR = 1.06, 95% CI [.94, 1.20]). A significant risk for total stroke could be observed when the consumption of total red meat was above 50 g/day, processed red meat was just above 0 g/day, and fresh red meat was above 70 g/day. Conclusion Our findings indicate that high consumption of red meat, especially processed red meat, will increase the risk of stroke.
- Published
- 2015
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