110 results on '"Chen, Yan"'
Search Results
2. Identification of serum MiRNAs as candidate biomarkers for non-small cell lung cancer diagnosis
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Zhang, Xintong, Tan, Jinjing, Chen, Yan, Ma, Shang, Bai, Wanqiu, Peng, Yanjing, and Shi, Guangli
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- 2022
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3. Circulating micrornas as potential diagnostic biomarkers for cervical intraepithelial neoplasia and cervical cancer: a systematic review and meta-analysis.
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Li, Yue, Zhu, Longbiao, Zhu, Chenjing, Chen, Yan, Yu, Hui, Zhu, Hangju, Yin, Ping, Liu, Mengyu, Li, Yang, Li, Huixin, Gong, Zhen, Hanzi Xu, and Han, Jing
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CERVICAL intraepithelial neoplasia ,CERVICAL cancer ,RANDOM effects model ,MICRORNA ,BIOMARKERS - Abstract
Background: Cervical cancer is a prevalent malignancy of the female reproductive system. Cervical intraepithelial neoplasia (CIN) is a precursor lesion for CC. Various studies have examined circulating microRNAs (miRNAs) as potential early diagnostic markers for CC and CIN. However, the findings have been inconclusive. Therefore, it is necessary to evaluate the diagnostic accuracy and identify potential sources of variability among these studies. Methods: The PubMed, Cochrane Library, Embase, and Web of Science databases were searched to identify relevant literature. Then, Stata 14.0 was utilized to calculate summary estimates for diagnostic parameters, including sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the summary receiver operating characteristic (ROC). To scrutinize the heterogeneity, the Cochran-Q test and I
2 statistic were utilized. As significant heterogeneity was observed, the random effects model was chosen. To explore potential sources of the heterogeneity, subgroup and regression analyses were conducted. Results: We analysed 12 articles reporting on 24 studies involving 1817 patients and 1731 healthy controls. The pooled sensitivity was 0.77 (95% CI 0.73–0.81), the specificity was 0.81 (95% CI 0.73–0.86), the PLR was 3.99 (95% CI 2.81–5.65), the NLR was 0.28 (95% CI 0.23–0.35), the DOR was 14.18 (95% CI 8.47–23.73), and the area under the curve (AUC) was 0.85 (95% CI 0.81–0.87). Subgroup analysis revealed that multiple miRNAs can improve diagnostic performance; the pooled sensitivity of multiple miRNAs was 0.78 (95% CI 0.68–0.86), the specificity was 0.85 (95% CI 0.78–0.90), and the AUC was 0.89 (95% CI 0.86–0.91). Conclusion: This study suggested that circulating microRNAs may be biomarkers for early CC diagnosis. [ABSTRACT FROM AUTHOR]- Published
- 2024
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4. Drought-triggered repression of miR166 promotes drought tolerance in soybean.
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Chen Zhao, Jingjing Ma, Chen Yan, Yu Jiang, Yaohua Zhang, Yudan Lu, Ye Zhang, Suxin Yang, Xianzhong Feng, and Jun Yan
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DROUGHT tolerance ,MICRORNA ,AGRICULTURAL productivity ,PLANT hormones ,TRANSGENIC plants - Abstract
Drought stress limits agricultural productivity worldwide. Identifying and characterizing genetic components of drought stress-tolerance networks may improve crop resistance to drought stress. We show that the regulatory module formed by miR166 and its target gene, ATHB14-LIKE, functions in the regulation of drought tolerance in soybean (Glycine max). Drought stress represses the accumulation of miR166, leading to upregulation of its target genes. Optimal knockdown of miR166 in the stable transgenic line GmSTTM166 conferred drought tolerance without affecting yield. Expression of ABA signaling pathway genes was regulated by the miR166-mediated regulatory pathway, and ATHB14-LIKE directly activates some of these genes. There is a feedback regulation between ATHB14-LIKE and MIR166 genes, and ATHB14-LIKE inhibits MIR166 expression. These findings reveal that drought-triggered regulation of the miR166-mediated regulatory pathway increases plants drought resistance, providing new insights into drought stress regulatory network in soybean. [ABSTRACT FROM AUTHOR]
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- 2024
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5. Diagnostic Value of Circulating MicroRNAs for Endometriosis: a Meta-analysis
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Zhou, Ling, Chen, Yan, Gao, Jianhua, Shankar, Sandhya, and Zhang, Guangmei
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- 2020
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6. MicroRNA-mediated regulation of BM-MSCs differentiation into sweat gland-like cells: targeting NF-κB
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Chen, Yan, Li, Qiankun, Tan, Zhijun, Zhang, Cuiping, and Fu, Xiaobing
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- 2019
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7. The identification of N6-methyladenosine-related miRNAs predictive of hepatocellular carcinoma prognosis and immunotherapy efficacy.
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Zou, Renrui, Liu, Yaqian, Qiu, Sangsang, Lu, Ya, Chen, Yan, Yu, Hui, Zhu, Hangju, Zhu, Wenbo, Zhu, Longbiao, Feng, Jifeng, and Han, Jing
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GENE expression ,CANCER prognosis ,PEARSON correlation (Statistics) ,MICRORNA ,IMMUNE checkpoint proteins - Abstract
BACKGROUND: Hepatocellular carcinoma (HCC) has a high degree of malignancy and poor prognosis. N6-methyladenosine (m6A) modifications and microRNAs (miRNAs) play pivotal roles in tumorigenesis and development. However, the role of m6A-related miRNAs in HCC has not been clarified yet. This study aimed to identify the role of m6A-miRNAs in HCC prognosis through bioinformatics analysis. METHODS: The clinicopathological information and RNA sequencing data of 369 HCC tumor tissues and 49 tumor-adjacent tissues were downloaded from the TCGA database. A total of 23 m6A regulators were extracted to evaluated the m6A-related miRNAs using Pearson's correlation analysis. Then, we selected prognosis-related m6A-miRNAs using a univariate Cox regression model and used the consensus cluster analysis to explore the characteristics of the m6A-miRNAs. The coefficient of the least absolute shrinkage and selection operator (LASSO) Cox regression was applied to construct a prognostic risk score model. The receiver operated characteristic (ROC) analysis was applied to evaluate the prognostic value of the signature. The biological functions of targeted genes were predicted by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Then, to validate the potential predictive value for prognosis, the miRNA expression profiles from the GSE76903 and GSE6857 were used. Single sample Gene Set Enrichment Analysis (ssGSEA) and Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data (ESTIMATE) were applied to assess the immune microenvironment of HCC. Additionally, a meta-analysis was used to verify the prognostic value of the m6A-microRNAs. RT-PCR was applied to validated the expression of miRNAs in HCC tissues. Cell viability, transwell assay and RNA m6A dot blot assays of HCC cells was applied to access the function of miR-17-5p. RESULTS: The expression of 48 m6A-related miRNAs was identified and 17 prognostic m6A-miRNAs was discovered. The expression profile of those 17 miRNAs was divided into three clusters, and these clusters were associated with the tumor microenvironment (TME) and prognosis. The nine m6A-related miRNA signature was associated with the prognosis of HCC, the AUC of the ROC was 0.771(TCGA dataset), 0.788(GSE76903) and 0.646(GSE6857). The TME and the expression of immune checkpoint molecules were associated with the risk score. The meta-analysis also validated the prognostic value of the m6A-related miRNAs (miR182-5p (HR:1.58, 95%CI:1.04-2.40) and miR-17-5p (HR:1.58, 95%CI: 1.04–2.40)). The expression of miR-17-5p was upregulated in HCC tissues and miR-17-5p showed an oncogenic role in HCC cells. CONCLUSION: The clinical innovation is the use of m6A-miRNAs as biomarkers for predicting prognosis regarding immunotherapy response in HCC patients. [ABSTRACT FROM AUTHOR]
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- 2023
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8. Serum microRNA signatures and metabolomics have high diagnostic value in gastric cancer
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Liu, Hai-Ning, Wu, Hao, Tseng, Yu-Jen, Chen, Yan-Jie, Zhang, Dan-Ying, Zhu, Lin, Dong, Ling, Shen, Xi-Zhong, and Liu, Tao-Tao
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- 2018
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9. IRF8 and its related molecules as potential diagnostic biomarkers or therapeutic candidates and immune cell infiltration characteristics in steroid-induced osteonecrosis of the femoral head.
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Liang, Xue-Zhen, Liu, Xiao-Chen, Li, Song, Wen, Ming-Tao, Chen, Yan-Rong, Luo, Di, Xu, Bo, Li, Nian-Hu, and Li, Gang
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BIOMARKERS ,OSTEONECROSIS ,STEROIDS ,CELL physiology ,FEMUR head ,SIGNAL peptides ,PROTEIN microarrays ,MICRORNA ,GENE expression ,RESEARCH funding ,RECEIVER operating characteristic curves ,COMPUTER-assisted molecular modeling - Abstract
Purpose: Steroid-induced osteonecrosis of the femoral head (SONFH) was a refractory orthopedic hip joint disease in the young and middle-aged people, but the pathogenesis of SONFH remained unclear. We aimed to identify the potential genes and screen potential therapeutic compounds for SONFH. Methods: The microarray was obtained for blood tissue from the GEO database, and then it identifies differentially expressed genes (DEGs). The DEGs were analyzed to obtain the differences in immune cell infiltration. The gene functional enrichment analysis of SONFH was analyzed. The PPI of DEGs was identified through the STRING database, and the cluster modules and hub genes were ascertained using MCODE and CytoHubba, and the ROC curve of hub genes was analyzed, and the tissues distribution of hub genes was understood by the HPA, Bgee and BioGPS databases. The hub genes and target miRNAs and corresponding upstream lncRNAs were predicted by TargetScan, miRDB and ENCORI database. Subsequently, we used CMap, DGIdb and L1000FWD databases to identify several potential therapeutic molecular compounds for SONFH. Finally, the AutoDockTools Vina, PyMOL and Discovery Studio were employed for molecular docking analyses between compounds and hub genes. Results: The microarray dataset GSE123568 was obtained related to SONFH. There were 372 DEGs including 197 upregulated genes and 175 downregulated genes by adjusted P value < 0.01 and |log
2 FC|> 1. Several significant GSEA enrichment analysis and biological processes and KEGG pathway associated with SONFH were identified, which were significantly related to cytoskeleton organization, nucleobase-containing compound catabolic process, NOD-like receptor signaling pathway, MAPK signaling pathway, FoxO signaling pathway, neutrophil-mediated immunity, neutrophil degranulation and neutrophil activation involved in immune response. Activated T cells CD4 memory, B cells naïve, B cells memory, T cells CD8 and T cells gamma delta might be involved in the occurrence and development of SONFH. Three cluster modules were identified in the PPI network, and eleven hub genes including FPR2, LILRB2, MNDA, CCR1, IRF8, TYROBP, TLR1, HCK, TLR8, TLR2 and CCR2 were identified by Cytohubba, which were differed in bone marrow, adipose tissue and blood, and which had good diagnostic performance in SONFH. We identified IRF8 and 10 target miRNAs that was utilized including Targetsan, miRDB and ENCORI databases and 8 corresponding upstream lncRNAs that was revealed by ENCORI database. IRF8 was detected with consistent expression by qRT-PCR. Based on the CMap, DGIdb and L1000FWD databases, the 11 small molecular compounds that were most strongly therapeutic correlated with SONFH were estradiol, genistein, domperidone, lovastatin, myricetin, fenbufen, rosiglitazone, sirolimus, phenformin, vorinostat and vinblastine. All of 11 small molecules had good binding affinity with the IRF8 in molecular docking. Conclusion: The occurrence of SONFH was associated with a "multi-target" and "multi-pathway" pattern, especially related to immunity, and IRF8 and its noncoding RNA were closely related to the development of SONFH. The CMap, DGIdb and L1000FWD databases could be effectively used in a systematic manner to predict potential drugs for the prevention and treatment of SONFH. However, additional clinical and experimental research is warranted. [ABSTRACT FROM AUTHOR]- Published
- 2023
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10. Long non-coding RNA RPL34-AS1 ameliorates oxygen–glucose deprivation-induced neuronal injury via modulating miR-223–3p/IGF1R axis.
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Wei, Xin-ya, Zhang, Tian-qi, Suo, Rui, Qu, You-yang, Chen, Yan, and Zhu, Yu-lan
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LINCRNA ,INSULIN-like growth factor receptors ,SOMATOMEDIN C ,BCL-2 proteins ,MICRORNA - Abstract
Ribosomal protein L34-antisense RNA 1 (RPL34-AS1), one of the long non-coding RNAs (lncRNAs), plays an important function in regulating diverse human malignant tumors. Nevertheless, the functions of RPL34-AS1 in ischemic stroke remain unclear. The present work focused on determining the candidate targets of RPL34-AS1 and its related mechanism in ischemic injury. The oxygen–glucose deprivation (OGD/R) in vitro cell model and middle cerebral artery occlusion (MCAO) in vivo rat model were utilized to simulate the pathological process of ischemic stroke. Additionally, the CCK8, WB (detecting Bcl-2 and Bax protein levels), and caspase-3 activity assays were done to investigate the anti-apoptotic functions of RPL34-AS1. The relationship among RPL34-AS1, insulin-like growth factor 1 receptor (IGF1R), and microRNA-223-3p (miR-223-3p) was determined through luciferase reporter assay. In this study, RPL34-AS1 expression was reduced in patients suffering from ischemic stroke. The overexpression of RPL34-AS1 reduced ischemic brain damage. However, the cell viability and glucose uptake were increased, and the apoptosis rate was decreased in the OGD/R-induced neurons. Further, miR-223-3p resulted in the decreased cell viability and glucose uptake and the increased cell apoptosis to cause ischemic brain damage. Besides, the neuroprotective effects of RPL34-AS1 on OGD/R injury were partly reversed by miR-223–3p. Mechanistically, lncRNA RPL34-AS1 could function as the competing endogenous RNA (ceRNA) of miR-223-3p to regulate IGF1R. Collectively, our study demonstrated that lncRNA RPL34-AS1 attenuated OGD/R-induced neuronal injury by mediating miR-223-3p/IGF1R axis. This discovery might serve as the candidate therapeutic target for ischemic stroke. [ABSTRACT FROM AUTHOR]
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- 2022
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11. The proliferation role of LH on porcine primordial germ cell‐like cells (pPGCLCs) through ceRNA network construction
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Wei Shen, Shun-Feng Cheng, Yu Tian, Hong-Chen Yan, Bao-Quan Han, Zi-Hui Yan, Wei Ge, Ming-Yu Zhang, and Shu-Er Zhang
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LH ,ceRNA network ,Medicine (General) ,Swine ,proliferation ,Medicine (miscellaneous) ,Biology ,R5-920 ,microRNA ,Animals ,Hippo Signaling Pathway ,Research Articles ,Hippo signalling pathway ,Cell Proliferation ,pPGCLCs ,Competing endogenous RNA ,Mechanism (biology) ,Stem Cells ,Transdifferentiation ,Luteinizing Hormone ,Hedgehog signaling pathway ,Cell biology ,Signalling ,Germ Cells ,Molecular Medicine ,RNA, Long Noncoding ,Stem cell ,Transcriptome ,Hormone ,Research Article - Abstract
Background The transdifferentiation of skin‐derived stem cells (SDSCs) into primordial germ cell‐like cells (PGCLCs) is one of the major breakthroughs in the field of stem cells research in recent years. This technology provides a new theoretical basis for the treatment of human infertility. However, the transdifferentiation efficiency of SDSCs to PGCLCs is very low, and scientists are still exploring ways to improve this efficiency or promote the proliferation of PGCLCs. This study aims to investigate the molecular mechanism of luteinising hormone (LH) to enhance porcine PGCLCs (pPGCLCs) proliferation. Results In this study, we dissected the proliferation regulatory network of pPGCLCs by whole transcriptome sequencing, and the results showed that the pituitary‐secreted reproductive hormone LH significantly promoted the proliferation of pPGCLCs. We combined whole transcriptome sequencing and related validation experiments to explore the mechanism of LH on the proliferation of pPGCLCs, and found that LH could affect the expression of Hippo signalling pathway‐related mRNAs, miRNAs and lncRNAs in pPGCLCs. Conclusions For the first time, we found that LH promotes pPGCLCs proliferation through the competing endogenous RNA (ceRNA) regulatory networks and Hippo signalling pathway. This finding may help to elucidate the molecular mechanism by which LH promotes pPGCLCs proliferation., LH promotes the proliferation of pPGCLCs in vitro.LH‐stimulated proliferation is accompanied by decreased apoptosis.Hippo signalling pathway‐associated ceRNA networks played an important role in the proliferation of pPGCLCs.
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- 2021
12. An immune-related microRNA signature prognostic model for pancreatic carcinoma and association with immune microenvironment.
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Shen, Qian, Li, JunChen, Pan, Xue, Zhang, ChuanLong, Jiang, XiaoChen, Li, Yi, Chen, Yan, and Pang, Bo
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PROGNOSTIC models ,GENE regulatory networks ,MICRORNA ,RECEIVER operating characteristic curves ,IMMUNE checkpoint proteins ,SURVIVAL analysis (Biometry) ,RANK correlation (Statistics) - Abstract
To establish a prognostic model based on immune-related microRNA (miRNA) for pancreatic carcinoma. Weighted correlation network analysis (WGCNA) was performed using the "WGCNA" package to find the key module genes involved in pancreatic carcinoma. Spearman correlation analysis was conducted to screen immune-related miRNAs. Uni- and multi-variate COX regression analyses were carried out to identify miRNAs prognostic for overall survival (OS) of pancreatic carcinoma, which were then combined to generate a prognostic model. Kaplan–Meier survival analysis, receiver operating characteristic (ROC) analysis, distribution plot of survival status in patients and regression analysis were collectively performed to study the accuracy of the model in prognosis. Target genes of the miRNAs in the model were intersected with the key module genes, and a miRNA–mRNA network was generated and visualized by Cytoscape3.8.0. TIMER analysis was conducted to study the abundance of immune infiltrates in tumor microenvironment of pancreatic carcinoma. Expression levels of immune checkpoint genes in subgroups stratified by the model were compared by Wilcoxon test. Gene Set Enrichment Analysis (GSEA) was performed to analyze the enriched signaling pathways between subgroups. Differential analysis revealed 1826 genes differentially up-regulated in pancreatic carcinoma and 1276 genes differentially down-regulated. A total of 700 immune-related miRNAs were obtained, of which 7 miRNAs were significantly associated with OS of patients and used to establish a prognostic model with accurate predictive performance. There were 99 mRNAs overlapped from the 318 target genes of the 7 miRNAs and the key modules genes analyzed by WGCNA. Patient samples were categorized as high or low risk according to the prognostic model, which were significantly associated with dendritic cell infiltration and expression of immune checkpoint genes (TNFSF9, TNFRSF9, KIR3DL1, HAVCR2, CD276 and CD80). GSEA showed remarkably enriched signaling pathways in the two subgroups. This study identified an immune-related 7-miRNA based prognostic model for pancreatic carcinoma, which could be used as a reliable tool for prognosis. [ABSTRACT FROM AUTHOR]
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- 2022
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13. LINC00461 Regulates the Recurrence of Large B Cell Lymphoma through the miR-411-5p/BNIP3 Pathway.
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Sun, Shu-wen, Chen, Yan, Liao, Hui-juan, Zhang, Wei, Xu, Wen-ming, and He, Guo-qian
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RESEARCH , *IN vitro studies , *IN vivo studies , *B cell lymphoma , *MICRORNA , *APOPTOSIS , *DISEASE relapse , *STATISTICAL correlation - Abstract
Objective. To analyze the mechanism of LINC00461 regulating the recurrence of diffuse large B cell lymphoma (DLBCL) through microRNA (miR)-411-5p/BCL2 interacting protein 3 (BNIP3) pathway. Methods. DLBCL samples in TCGA and GSE12453 were used for differential analysis to find long noncoding RNA (lncRNA) related to DLBCL recurrence. The 4 DLBCL data with the highest and lowest expression levels of LINC00461 in the TCGA database were selected for GSEA enrichment analysis. The targeting relationships of miR-411-5p with LINC00461 and BNIP3 were verified by the dual luciferase report. Blood samples from DLBCL patients were used to analyze the correlation between miR-411-5p and LINC00461 or BNIP3. LINC00461, miR-411-5p, or BNIP3 was overexpressed or silenced by transfection, and a tumor-bearing nude mice model was constructed to detect their effects on proliferation and apoptosis. Results. The level of LINC00461 in DLBCL was significantly higher than that in normal cases, and the level in recurrence DLBCL was significantly higher than that in nonrecurrence. The enrichment analysis results showed that the function of LINC00461 was closely related to apoptosis. The results shown that miR-411-5p bound to LINC00461 and BNIP3 and was negatively correlated with LINC00461 and BNIP3 mRNA in blood of DLBCL patients. Suppressing the level of LINC00461 inhibited cell proliferation and induced apoptosis. The inhibition of LINC00461 or overexpression of miR-411-5p reduced the expression of BNIP3 protein, thereby inducing apoptosis at the in vivo and in vitro levels. Conclusion. LINC00461 may induce miR-411-5p to "sponge," thereby increasing the expression of BNIP3 protein, and exerting the function of inhibiting apoptosis and promoting DLBCL recurrence. [ABSTRACT FROM AUTHOR]
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- 2022
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14. Total Saponins of Radix Clematis Regulate Fibroblast-Like Synoviocyte Proliferation in Rheumatoid Arthritis via the LncRNA OIP5-AS1/MiR-410-3p/Wnt7b Signaling Pathway.
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Pan, Lingyu, Sun, Yuan, Jiang, Hui, Chen, Yan, Jiang, Yeke, Han, Yanquan, and Wang, Yongzhong
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BIOLOGICAL models ,PROTEIN kinases ,FIBROBLASTS ,SYNOVIAL membranes ,ANIMAL experimentation ,WESTERN immunoblotting ,GLYCOSIDES ,WNT proteins ,RNA ,MICRORNA ,CYTOSKELETAL proteins ,CELL cycle proteins ,CELLULAR signal transduction ,RATS ,RHEUMATOID arthritis ,CELL proliferation ,FLUORESCENT antibody technique ,PLANT extracts ,TRANSCRIPTION factors ,POLYMERASE chain reaction - Abstract
Background. Rheumatoid arthritis (RA) is the most common autoimmune disease and affects multiple joints. Previous studies have shown that total saponins of Radix clematidis (TSC) have a clear therapeutic effect on RA, but the specific mechanism has not yet been clarified. Literature screening and previous research suggest that the lncRNA OIP5-AS1/miR-410-3p/Wnt7b signaling pathway exerts a regulatory effect on the pathogenesis of RA. In this study, we examined whether the TSC treatment of RA affects the lncRNA OIP5-AS1/miR-410-3p/Wnt7b pathway. Materials and Methods. Freund's complete adjuvant was used to create an adjuvant arthritis (AA) rat model with rat synovial cells being harvested and cultured. The experiment comprises a normal group, model group, TSC optimal-dose group, TSC optimal-dose group + lncRNA OIP5-AS1siRNA group, lncRNA OIP5-AS1 siRNA group, and lncRNA OIP5-AS1 siRNA + NC group. MMT was used to screen the optimal concentration of TSC. The level of lncRNA OIP5-AS1, miR-410-3p, Wnt7b, β-catenin, c-Myc, cyclin D1, GSK-3β, and SFRP4 mRNA were detected by real-time-qPCR, the expression of Wnt7b, β-catenin, c-Myc, cyclin D1, GSK-3β, and p-GSK-3β (Ser9) protein were detected by immunofluorescence and Western blot. Results. We found that TSC inhibits the proliferation of RA FLS, TSC significantly reduced lncRNA OIP5-AS1, Wnt7b, β-catenin, c-Myc, cyclin D1, and p-GSK-3β/GSK-3β mRNA/protein expression, whereas the miR-410-3p and SFRP4 mRNA/protein expression levels were significantly upregulated. Our data suggest that TSC can inhibit the excessive proliferation of FLS to treat RA, the mechanism of which may be closely related to regulation of the lncRNA OIP5-AS1/miR-410-3p /Wnt7b signaling axis and the Wnt signaling pathway. [ABSTRACT FROM AUTHOR]
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- 2022
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15. Overexpression of SP1 restores autophagy to alleviate acute renal injury induced by ischemia-reperfusion through the miR-205/PTEN/Akt pathway.
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Huang, Chong, Chen, Yan, Lai, Bin, Chen, Yan-Xia, Xu, Cheng-Yun, and Liu, Yuan-Fei
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ACUTE kidney failure ,AUTOPHAGY ,KIDNEY tubules ,MICRORNA ,WOUNDS & injuries - Abstract
Background: Acute kidney injury (AKI) is a major kidney disease with poor clinical outcome. SP1, a well-known transcription factor, plays a critical role in AKI and subsequent kidney repair through the regulation of various cell biologic processes. However, the underlying mechanism of SP1 in these pathological processes remain largely unknown. Methods: An in vitro HK-2 cells with anoxia-reoxygenation injury model (In vitro simulated ischemic injury disease) and an in vivo rat renal ischemia-reperfusion injury model were used in this study. The expression levels of SP1, miR-205 and PTEN were detected by RT-qPCR, and the protein expression levels of SP1, p62, PTEN, AKT, p-AKT, LC3II, LC3I and Beclin-1 were assayed by western blot. Cell proliferation was assessed by MTT assay, and the cell apoptosis was detected by flow cytometry. The secretions of IL-6 and TNF-α were detected by ELISA. The targeted relationship between miR-205 and PTEN was confirmed by dual luciferase report assay. The expression and positioning of LC-3 were observed by immunofluorescence staining. TUNEL staining was used to detect cell apoptosis and immunohistochemical analysis was used to evaluate the expression of SP1 in renal tissue after ischemia-reperfusion injury in rats. Results: The expression of PTEN was upregulated while SP1 and miR-205 were downregulated in renal ischemia-reperfusion injury. Overexpression of SP1 protected renal tubule cell against injury induced by ischemia-reperfusion via miR-205/PTEN/Akt pathway mediated autophagy. Overexpression of SP1 attenuated renal ischemia-reperfusion injury in rats. Conclusions: SP1 overexpression restored autophagy to alleviate acute renal injury induced by ischemia-reperfusion through the miR-205/PTEN/Akt pathway. [ABSTRACT FROM AUTHOR]
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- 2021
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16. MicroRNAs and cancer
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Xiao, Libo, Wu, Zhiping, Feng, Rui, Zhu, Qishun, Gao, Chenwei, Chen, Yan, Hou, Chun, and Wu, Yonggui
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- 2010
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17. circCUL3 drives malignant progression of cervical cancer by activating autophagy through sponge miR-223-3p upregulation of ATG7.
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Qin, Jiahui, Chen, Yan, Zhao, Xia, and Yu, Jingmin
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MICRORNA , *CERVICAL cancer , *AUTOPHAGY , *CIRCULAR RNA , *CANCER invasiveness - Abstract
• CircCUL3 overexpression drives cervical cancer progression. • CircCUL3 acts as a sponge for miR-223-3p to upregulate ATG7 and activate autophagy. • Chloroquine reverses circCUL3-induced effects by restoring miR-223-3p expression. Circular RNA (circRNA) has emerged as a pivotal regulatory factor in cancer biology, yet its exact role in cervical cancer remains incompletely understood. In this study, we investigated the functional role of circCUL3 in cervical cancer and explored its potential as a therapeutic target. Functional gain and loss experiments were conducted in Hela and Siha cell lines to elucidate the biological functions of circCUL3 in cervical cancer. The results revealed that circCUL3 overexpression significantly enhanced cell viability, migration, and invasion while suppressing apoptosis, while circCUL3 knockout displayed the opposite effects. Mechanistically, we identified hsa-miR-223-3p as a target of circCUL3, with its expression being negatively regulated by circCUL3. Furthermore, we discovered that circCUL3 could sequester miR-223-3p, leading to the upregulation of ATG7 expression, and this was linked to the regulation of autophagy in cervical cancer cells. In vivo validation using a xenograft mouse model further supported our in vitro findings. Notably, we found that chloroquine (CQ), an autophagy inhibitor, restored miR-223-3p expression and counteracted the oncogenic effect of circCUL3 overexpression. In conclusion, circCUL3 potentially contributes to the malignant progression of cervical cancer by acting as a sponge for miR-223-3p, resulting in the upregulation of ATG7 and the activation of autophagy. [ABSTRACT FROM AUTHOR]
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- 2024
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18. MiR-199a-3p affects the multi-chemoresistance of osteosarcoma through targeting AK4
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Liu Kai, Bian Yujun, Wang Lei, Dai Yong, Jiang Ya, and Chen Yan
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Male ,0301 basic medicine ,Cancer Research ,miR-199a-3p ,AK4 ,Mice, Nude ,Adenylate kinase ,Bone Neoplasms ,Drug resistance ,Biology ,lcsh:RC254-282 ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Western blot ,Surgical oncology ,Cell Line, Tumor ,microRNA ,Genetics ,medicine ,Animals ,Humans ,Gene ,Osteosarcoma ,medicine.diagnostic_test ,Adenylate Kinase ,Multi-chemoresistance ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Drug Resistance, Multiple ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,030104 developmental biology ,Oncology ,Drug Resistance, Neoplasm ,030220 oncology & carcinogenesis ,Cancer research ,Heterografts ,Signal transduction ,Research Article - Abstract
Background MicroRNAs (miRNAs) play vital roles in regulating various biological processes. The dysregulations of miRNAs may result in severe human diseases, including cancer. Methods We performed the qRT-PCR, western blot and the luciferase reporter assays to test whether Adenylate Kinase 4 (AK4) is the target of miR-199a-3p. Up- or down-regulation of miR-199a-3p and/or the AK4 gene was done to detect their roles in OS multi-drug resistance using drug resistance profiling assays. We further predicted the putative signal pathway involved in the miR-199a-3p-mediated OS drug-resistance. Results The AK4 gene is one of the targets of miR-199a-3p and negatively correlates with the effect of miR-199a-3p on OS drug-resistance. In addition, the activity of the NF-кB signaling pathway was drastically altered by the forced changes of the miR-199a-3p level in OS cells. Conclusions Our data revealed that both miR-199a-3p and its target gene AK4 are reversely correlated with the OS drug resistance. Electronic supplementary material The online version of this article (10.1186/s12885-018-4460-0) contains supplementary material, which is available to authorized users.
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- 2018
19. Construction of miRNA-mRNA-TF Regulatory Network for Diagnosis of Gastric Cancer.
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Fu, Zhenjie, Xu, Yuqin, Chen, Yan, Lv, Hang, Chen, Guiping, and Chen, Yitao
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STOMACH tumors ,REVERSE transcriptase polymerase chain reaction ,REFERENCE values ,MOLECULAR diagnosis ,SEQUENCE analysis ,GENETIC mutation ,WESTERN immunoblotting ,MICRORNA ,METABOLISM ,MESSENGER RNA ,GENE expression profiling ,GENES ,TRANSCRIPTION factors ,POLYMERASE chain reaction - Abstract
Gastric cancer (GC), as an epidemic cancer worldwide, has more than 1 million new cases and an estimated 769,000 deaths worldwide in 2020, ranking fifth and fourth in global morbidity and mortality. In mammals, both miRNAs and transcription factors (TFs) play a partial role in gene expression regulation. The mRNA expression profile and miRNA expression profile of GEO database were screened by GEO2R for differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs). Then, DAVID annotated the functions of DEGs to understand the functions played in biological processes. The prediction of potential target genes of miRNA and key TFs of mRNA was performed by mipathDB V2.0 and CHEA3, respectively, and the gene list comparison was performed to look for overlapping genes coregulated by key TFs and DEMs. Finally, the obtained miRNAs, TF, and overlapping genes were used to construct the miRNA-mRNA-TF regulatory network, which was verified by RT-qPCR. 76 upregulated DEGs, 199 downregulated DEGs, and 3 upregulated miRNAs (miR-199a-3p/miR-199b-3p, miR-125b-5p, and miR-199a-5p) were identified from the expression profiles of mRNA (GSE26899, GSE29998, GSE51575, and GSE13911) and miRNA (GSE93415), respectively. Through database prediction and gene list comparison, it was found that among the 199 downregulated DEGs, 61, 71, and 69 genes were the potential targets of miR-199a-3p/miR-199b-3p, miR-125b-5p, and miR-199a-5p, respectively. 199 downregulated DEGs were used as the gene list for the prediction of key TFs, and the results showed that RFX6 ranked the highest. The potential target overlap genes of miR-199a-3p/miR-199b-3p, miR-125b-5p, and miR-199a-5p were 4 genes (SH3GL2, ATP4B, CTSE, and SORBS2), 7 genes (SLC7A8, RNASE4, ESRRG, PGC, MUC6, Fam3B, and FMO5), and 6 genes (CHGA, PDK4, TMPRSS2, CLIC6, GPX3, and PSCA), respectively. Finally, we constructed a miRNA-mRNA-TF regulatory network based on the above 17 mRNAs, 3 miRNAs, and 1 TF and verified by RT-qPCR and western blot results that the expression of RFX6 was downregulated in GC tissues. These identified miRNAs, mRNAs, and TF have a certain reference value for further exploration of the regulatory mechanism of GC. [ABSTRACT FROM AUTHOR]
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- 2021
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20. PVT1‐derived miR‐1207‐5p promotes breast cancer cell growth by targeting STAT6
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Yunde Liu, Qingjuan Yao, Weiwei Kong, Yaqing Chen, Liya Fu, Chen Yan, and Yuhua Yuan
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0301 basic medicine ,Cancer Research ,medicine.drug_class ,Carcinogenesis ,Breast Neoplasms ,Biology ,Cell Line ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Cell Movement ,Cell Line, Tumor ,microRNA ,medicine ,Humans ,Breast ,PVT1 ,STAT6 ,Cell growth ,Cell Cycle ,miR‐1207‐5p ,General Medicine ,Original Articles ,Cell cycle ,Middle Aged ,medicine.disease ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,030104 developmental biology ,cell proliferation ,Cell Transformation, Neoplastic ,HEK293 Cells ,Oncology ,Estrogen ,030220 oncology & carcinogenesis ,Cancer research ,Ectopic expression ,Original Article ,RNA, Long Noncoding ,CDKN1B ,STAT6 Transcription Factor - Abstract
Accumulating evidence indicates that ectopic expression of non-coding RNAs are responsible for breast cancer progression. Increased non-coding RNA PVT1, the host gene of microRNA-1207-5p (miR-1207-5p), has been associated with breast cancer proliferation. However, how PVT1 functions in breast cancer is still not clear. In this study, we show a PVT1-derived microRNA, miR-1207-5p, that promotes the proliferation of breast cancer cells by directly regulating STAT6. We first confirm the positive correlated expression pattern between PVT1 and miR-1207-5p by observing consistent induced expression by estrogen, and overexpression in breast cancer cell lines and breast cancer patient specimens. Moreover, silence of PVT1 also decreased miR-1207-5p expression. Furthermore, increased miR-1207-5p expression promoted, while decreased miR-1207-5p expression suppressed, cell proliferation, colony formation, and cell cycle progression in breast cancer cell lines. Mechanistically, a novel target of miR-1207-5p, STAT6, was identified by a luciferase reporter assay. Overexpression of miR-1207-5p decreased the levels of STAT6, which activated CDKN1A and CDKN1B to regulate the cell cycle. We also confirmed the reverse correlation of miR-1207-5p and STAT6 expression levels in breast cancer samples. Therefore, our findings reveal that PVT1-derived miR-1207-5p promotes the proliferation of breast cancer cells by targeting STAT6, which in turn controls CDKN1A and CDKN1B expression. These findings suggest miR-1207-5p might be a potential target for breast cancer therapy.
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- 2017
21. MicroRNA-513b-5p targets COL1A1 and COL1A2 associated with the formation and rupture of intracranial aneurysm.
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Zheng, Zheng, Chen, Yan, Wang, Yinzhou, Li, Yongkun, and Cheng, Qiong
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MICRORNA , *INTRACRANIAL aneurysms , *PROTEIN expression , *POLYMERASE chain reaction , *VASCULAR smooth muscle - Abstract
Collagen-type I alpha 1 chain (COL1A1) and COL1A2 are abnormally expressed in intracranial aneurysm (IA), but their mechanism of action remains unclear. This study was performed to investigate the mechanism of COL1A1 and COL1A2 affecting the occurrence and rupture of IA. Quantitative real-time polymerase chain reaction was used to measure the expression of hsa-miR-513b-5p, COL1A1, COL1A2, TNF-α, IL-6, MMP2, MMP3, MMP9 and TIMP4 in patients with ruptured IA (RA) (n = 100), patients with un-ruptured IA (UA) (n = 100), and controls (n = 100). Then, human vascular smooth muscle cells (HASMCs) were cultured, and dual luciferase reporter assay was performed to analyse the targeting relationship between miR-513b-5p and COL1A1 or COL1A2. The effects of the miR-513b-5p mimic and inhibitor on the proliferation, apoptosis, and death of HASMC and the RIP1-RIP3-MLKL and matrix metalloproteinase pathways were also explored. The effect of silencing and over-expression of COL1A1 and COL1A2 on the role of miR-513b-5p were also evaluated. Finally, the effects of TNF-α on miR-513b-5p targeting COL1A1 and COL1A2 were tested. Compared with those in the control group, the serum mRNA levels of miR-513b-5p, IL-6 and TIMP4 were significantly decreased in the RA and UA groups, but COL1A1, COL1A2, TNF-α, IL-1β, MMP2, MMP3 and MMP9 were significantly increased (p < 0.05). Compared with those in the UA group, the expression of COL1A1, COL1A2, TNF-α, IL-1β and MMP9 was significantly up-regulated in the RA group (p < 0.05). Results from the luciferase reporter assay showed that COL1A1 and COL1A were the direct targets of miR-513b-5p. Further studies demonstrated that miR-513b-5p targeted COL1A1/2 to regulate the RIP1-RIP3-MLKL and MMP pathways, thereby enhancing cell death and apoptosis. Over-expression of COL1A1 or COL1A2, rather than silencing COL1A1/2, could improve the inhibitory effect of miR-513b-5p on cell activity by regulating the RIP1-RIP3-MLKL and MMP pathways. Furthermore, over-expression of miR-513b-5p and/or silencing COL1A1/2 inhibited the TNF-α-induced cell proliferation and enhanced the TNF-α-induced cell death and apoptosis. The mechanism may be related to the inhibition of collagen I and TIMP4 expression and promotion of the expression of RIP1, p-RIP1, p-RIP3, p-MLKL, MMP2 and MMP9. MiR-513b-5p targeted the inhibition of COL1A1/2 expression and affected HASMC viability and extracellular mechanism remodelling by regulating the RIP1-RIP3-MLKL and MMP pathways. This process might be involved in the formation and rupture of IA. [ABSTRACT FROM AUTHOR]
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- 2021
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22. A compact fiber-integrated optofluidic platform for highly specific microRNA Förster resonance energy transfer detection.
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Feng, Hongtao, Liu, Lin, Chen, Yi, Shu, Weiliang, Huang, Yuqing, Zhang, Baoyue, Wu, Tianzhun, Jin, Zongwen, and Chen, Yan
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FLUORESCENCE resonance energy transfer ,MICRORNA - Abstract
MicroRNAs (miRNAs) have attracted extensive interest as promising biomarkers for the profiling of diseases. However, quantitative measurement of miRNAs presents a significant challenge in biochemical studies. In this work, we developed an innovative optofluidic platform to perform a rapid, simple, quantitative and high-specificity miRNA assay using the Förster resonance energy transfer (FRET) principle. A novel three-way junction FRET probe was proposed to enable rapid and enzyme-free miRNA detection. Using this platform, we performed one-step, amplification-free miRNA detection with simple device operation and achieved miRNA identification at a low concentration. The detection system could achieve high specificity for discrimination of three-base mismatches, and the sample volume was significantly reduced, favorable for low-level miRNA detection in material-limited samples. The establishment of a compact, low-cost, highly sensitive and selective miRNA analysis platform provides a valuable tool for point-of-care diagnosis. [ABSTRACT FROM AUTHOR]
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- 2021
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23. MicroRNAs Regulating Mitochondrial Function in Cardiac Diseases.
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Zhang, Guang-Qiong, Wang, Sheng-Quan, Chen, Yan, Fu, Ling-Yun, Xu, Yi-Ni, Li, Ling, Tao, Ling, and Shen, Xiang-Chun
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HEART diseases ,NON-coding RNA ,MICRORNA ,MITOCHONDRIA ,MECHANICAL hearts - Abstract
Mitochondria are the key organelles that supply cellular energy. As the most active organ in the body, the energy required to maintain the mechanical function of the heart requires a high quantity of high-quality mitochondria in cardiomyocytes. MicroRNAs (miRNAs) are single-stranded noncoding RNAs, approximately 22 nt in length, which play key roles in mediating post-transcriptional gene silencing. Numerous studies have confirmed that miRNAs can participate in the occurrence and development of cardiac diseases by regulating mitochondrial function-related genes and signaling pathways. Therefore, elucidating the crosstalk that occurs between miRNAs and mitochondria is important for the prevention and treatment of cardiac diseases. In this review, we discuss the biogenesis of miRNAs, the miRNA-mediated regulation of major genes involved in the maintenance of mitochondrial function, and the effects of miRNAs on mitochondrial function in cardiac diseases in order to provide a theoretical basis for the clinical prevention and treatment of cardiac disease and the development of new drugs. [ABSTRACT FROM AUTHOR]
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- 2021
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24. Ago2 and Dicer1 are involved in METH-induced locomotor sensitization in mice via biogenesis of miRNA.
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Liu, Dan, Zhu, Li, Ni, Tong, Guan, Fang‐lin, Chen, Yan‐jiong, Ma, Dong‐liang, Goh, Eyleen L.K., Chen, Teng, Guan, Fang-Lin, Chen, Yan-Jiong, and Ma, Dong-Liang
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MICRORNA ,NUCLEUS accumbens ,REGULATOR genes ,DRUG addiction ,RNA metabolism ,ANIMAL experimentation ,BASAL ganglia ,BIOCHEMISTRY ,CARRIER proteins ,COMPARATIVE studies ,ESTERASES ,HUMAN locomotion ,PHENOMENOLOGY ,RESEARCH methodology ,MEDICAL cooperation ,METHAMPHETAMINE ,MICE ,RESEARCH ,SUBSTANCE abuse ,TRANSFERASES ,EVALUATION research ,CENTRAL nervous system stimulants ,PHARMACODYNAMICS - Abstract
microRNA (miRNA) play important roles in drug addiction and act as a post-transcriptional regulator of gene expression. We previously reported extensive downregulation of miRNAs in the nucleus accumbens (NAc) of methamphetamine (METH)-sensitized mice. However, the regulatory mechanism of this METH-induced downregulation of miRNAs has yet to be elucidated. Thus, we examined METH-induced changes in the expression of miRNAs and their precursors, as well as the expression levels of mRNA and the proteins involved in miRNA biogenesis such as Dicer1 and Ago2, in the nucleus accumbens of METH-induced locomotor sensitized mice. miRNAs and Ago2 were significantly downregulated, while the expression of miRNA precursors remained unchanged or upregulated, which suggests that the downregulation of miRNAs was likely due to a reduction in Ago2-mediated splicing but unlikely to be regulated at the transcription level. Interestingly, the expression level of Dicer1, which is a potential target of METH-induced decreased miRNAs, such as miR-124, miR-212 and miR-29b, was significantly increased. In conclusion, this study indicates that miRNA biogenesis (such as Ago2 and Dicer1) and their miRNA products may have a role in the development of METH addiction. [ABSTRACT FROM AUTHOR]
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- 2019
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25. Circulating Epstein‐Barr virus microRNAs BART7‐3p and BART13‐3p as novel biomarkers in nasopharyngeal carcinoma.
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Lu, Tianzhu, Guo, Qiaojuan, Lin, Keyu, Chen, Honglin, Chen, Yixin, Xu, Yuanji, Lin, Cheng, Su, Ying, Chen, Yan, Chen, Mengyuan, Zheng, Yuhong, Ye, Yunbin, Lin, Shaojun, Zong, Jingfeng, and Pan, Jianji
- Abstract
Epstein‐Barr virus (EBV) BamHI A rightward transcripts (BART) encoded microRNAs (EBV‐miR‐BARTs) are abnormally highly expressed in nasopharyngeal carcinoma (NPC). This study aims to investigate the diagnostic and prognostic performance of miR‐BART7‐3p and miR‐BART13‐3p. Plasma levels of EBV DNA, miR‐BART7‐3p, and miR‐BART13‐3p were examined by quantitative PCR in 483 treatment‐naïve NPC patients and 243 controls without NPC. The prognostic performance was examined by comparing plasma levels with rates of distant metastasis during follow‐up. The area under the receiver operating characteristic curve for diagnosing NPC was 0.926 for EBV DNA, 0.964 for plasma miR‐BART7‐3p, 0.973 for miR‐BART13‐3p, and 0.997 for all three indices. Among 465 NPC patients without distant metastasis, the above‐median miR‐BART7‐3p and EBV DNA were independent risk for shorter distant metastasis‐free survival (DMFS) (hazard ratio [HR] = 2.94, 95% confidence interval [CI], 1.44‐5.97, P =.003; HR = 2.27, 95% CI, 1.26‐4.10, P =.006) in multivariate Cox regression. Epstein‐Barr virus DNA, miR‐BART7‐3p, and miR‐BART13‐3p after radiotherapy were detectable in 28.6%, 17.6%, and 54.7% of patients, respectively. In multivariate Cox regression, detectable miR‐BART7‐3p and EBV DNA were independent risks for shorter DMFS (HR = 4.13, 95% CI, 1.89‐9.01, P <.001; HR = 2.14, 95% CI, 1.04‐4.42, P =.039). The 4‐year DMFS rate was 92.0% in subjects (n = 156) with neither detectable miR‐BART7‐3p nor EBV DNA, 80.0% in subjects (n = 65) with either detectable miR‐BART7‐3p or EBV DNA, and 52.9% in subjects (n = 24) with both detectable miR‐BART7‐3p and EBV DNA after radiotherapy (P <.001). Circulating levels of miR‐BART7‐3p and miR‐BART13‐3p show excellent diagnostic performance for NPC. The combination of plasma levels of miR‐BART7‐3p and EBV DNA at diagnosis and after radiotherapy could help stratify patients by risk of poor DMFS. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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26. MicroRNA‐425‐5p promotes breast cancer cell growth by inducing PI3K/AKT signaling.
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Zhang, Li‐Feng, Zhang, Ji‐Gang, Zhou, Hao, Dai, Tian‐Tian, Guo, Feng‐Bao, Xu, Shao‐Yong, and Chen, Yan
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CANCER cell growth ,BREAST cancer ,BREAST cancer prognosis ,MICRORNA ,PTEN protein ,PHOSPHATIDYLINOSITOL 3-kinases ,PROTEIN kinase B - Abstract
MicroRNA‐425‐5p (miR‐425‐5p) has been reported to be involved in the tumorigenesis of several tumors, but its function in breast cancer is still unknown. In this study, miR‐425‐5p was found significantly upregulated in breast cancer cells, and predicted a poor prognosis for breast cancer patients. Overexpression of miR‐425‐5p could significantly promote breast cancer cell growth. Further studies showed that overexpression of miR‐425‐5p upregulated the protein levels of Cyclin D1, Cyclin D3, CDK4, and CDK6. However, inhibiting miR‐425‐5p downregulated their expression and induced cell cycle arrest at G0/G1 phase. In mechanism, overexpression of miR‐425‐5p increased the phosphorylation of PI3K p85 and AKT, but inhibiting miR‐425‐5p displayed opposite effects. Moreover, miR‐425‐5p bound to the 3'UTR of PTEN mRNA, and downregulated the expression levels of PTEN in both mRNA and protein levels in breast cancer cells. Collectively, the results above demonstrated that miR‐425‐5p was involved in the tumorigenesis of breast cancer by inducing PI3K/AKT signaling and indicated that miR‐425‐5p could be as a potential target for breast cancer therapy in the future. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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27. Genome-wide identification of miRNAs and their targets during early somatic embryogenesis in Dimocarpus longan Lour.
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Xu, Xiaoping, Chen, Xiaohui, Chen, Yan, Zhang, Qinglin, Su, Liyao, Chen, Xu, Chen, Yukun, Zhang, Zihao, Lin, Yuling, and Lai, Zhongxiong
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MICRORNA ,SOMATIC embryogenesis ,LONGAN ,LIGNINS ,NON-coding RNA - Abstract
miRNAs are endogenous regulatory factors that play pivotal roles in post-transcriptional regulation. However, their specific roles in early somatic embryogenesis (SE) remain unclear. Study of the SE system is fundamental for clarifying the molecular mechanisms in Dimocarpus longan. We identified 289 known miRNAs from 106 different miRNA families and 1087 novel miRNAs during early longan SE, including embryogenic callus (EC), incomplete pro-embryogenic culture (ICpEC), globular embryo (GE), and non-embryogenic callus (NEC). The abundances of known miRNAs were concentrated in GE. The differentially expression (DE) miRNAs showed five expression patterns during early SE. Largely miRNAs were expressed highly and specially in EC, ICpEC, and GE, respectively. Some miRNAs and putative target genes were enriched in lignin metabolism. Most potential targets were related to the pathways of plant hormone signal transduction, alternative splicing, tyrosine metabolism and sulfur metabolism in early longan SE. The regulatory relationships between dlo-miR166a-3p and DlHD-zip8, dlo-miR397a and DlLAC7, dlo-miR408-3p and DlLAC12 were confirmed by RNA ligase-mediated rapid amplification of cDNA ends. The expression patterns of eight DE miRNAs detected by qRT-PCR were consistent with RNA-seq. Finally, the miRNA regulatory network in early SE was constructed, which provided new insight into molecular mechanism of early SE in longan. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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28. Dynamic Changes of DNA Methylation and Transcriptome Expression in Porcine Ovaries during Aging.
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Xi, Xiaoyu, Zou, Qin, Wei, Yingying, Chen, Yan, Wang, Xue, Lv, Daojun, Li, Peilin, Wen, Anxiang, Zhu, Li, Tang, Guoqing, Ma, Jideng, Li, Mingzhou, Li, Xuewei, and Jiang, Yanzhi
- Subjects
OVARIAN physiology ,RNA analysis ,AGING ,ANIMAL experimentation ,APOPTOSIS ,CONCEPTION ,GENETIC research ,GENOMES ,HUMAN reproduction ,MESSENGER RNA ,OVARIES ,OVULATION ,PUBERTY ,SWINE ,FETAL development ,DNA methylation ,GENE expression profiling ,MICRORNA ,SEQUENCE analysis ,EVALUATION - Abstract
The biological function of human ovaries declines along with aging. To identify the underlying molecular changes during ovarian aging, pigs were used as model animals. Genome-wide DNA methylation and transcriptome-wide RNA expression analyses were performed via high-throughput sequencing of ovaries from young pigs (180 days, puberty stage of first ovulation) and old pigs (eight years, reproductive exhaustion stage). The results identified 422 different methylation regions between old and young pigs; furthermore, a total of 2,243 mRNAs, 95 microRNAs, 248 long noncoding RNAs (lncRNAs), and 116 circular RNAs (circRNAs) were differentially expressed during both developmental stages. Gene ontology analysis showed that these genes related to different methylation and expression are involved in the ovarian aging cycle. Specifically, these are involved in cell apoptosis, death effector domain binding, embryonic development, reproduction and fertilization process, ovarian cumulus expansion, and the ovulation cycle. Multigroup cooperative control relationships were also assessed, and competing endogenous RNA (ceRNA) networks were constructed in the ovarian aging cycle. These data will help to clarify ovary age-associated potential molecular changes in DNA methylation and transcriptional patterns over time. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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29. Rosiglitazone prevents acute pancreatitis through inhibiting microRNA-26a expression.
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Chen, Yan, Xiang, Wei, Li, Xiang, Wang, Daming, and Qian, Chunyan
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PTEN protein , *ROSIGLITAZONE , *AMYLASES , *WESTERN immunoblotting , *PANCREATITIS , *REPORTER genes , *MICRORNA - Abstract
The aim of the present study was to investigate the regulatory effect of rosiglitazone on the progression of acute pancreatitis (AP) and pancreas injury, and the underlying mechanism. An AP rat model was established using caerulein and validated by detection of amylase, lipase, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and transforming growth factor-β (TGF-β) serum levels. Pancreatic injury was assessed by pathological examination. The expression levels of microRNA (miR)-26a in AP rats and AR42J cells were analyzed using reverse transcription-quantitative PCR (RT-qPCR). Luciferase reporter gene assay was applied for detecting whether miR-26a bound to the target gene phosphatase and tensin homolog (PTEN). The regulatory effect of rosiglitazone on the PI3K/AKT signaling pathway was analyzed by western blot analysis. Results demonstrated that establishment of an AP model was successful with severe pancreas injury and classic AP phenotypes observed in rats. Increased serum expression of amylase, lipase, TNF-α, IL-6 and TGF-β were observed in AP rats. Rosiglitazone pretreatment prevented AP progression through suppression of miR-26a expression via binding to and degrading PTEN. Western blot analysis demonstrated that rosiglitazone blocked the PI3K/AKT signaling pathway through PTEN. In conclusion, it was determined that rosiglitazone prevented AP by downregulating miR-26a via the PI3K/AKT signaling pathway. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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30. miR-145 suppresses ovarian cancer progression via modulation of cell growth and invasion by targeting CCND2 and E2F3.
- Author
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Hua, Minhui, Qin, Yongwei, Sheng, Meihong, Cui, Xiaopeng, Chen, Weiguan, Zhong, Jianxin, Yan, Junming, and Chen, Yan
- Subjects
OVARIAN cancer treatment ,MICRORNA ,CANCER invasiveness ,CANCER cell growth ,TRANSCRIPTION factors ,NEOPLASTIC cell transformation - Abstract
MicroRNAs (miRNA/miRs) have been demonstrated to be critical post-transcriptional modulators of gene expression during tumorigenesis. Numerous miRNAs have been revealed to be downregulated in human epithelial ovarian cancer (EOC). In the present study, it was observed that the expression of miR-145 was decreased in EOC tissues and cell lines. Overexpression of miR-145 inhibited the proliferation, migration and invasion of EOC cells. The D-type cyclin 2, cyclin D2 (CCND2), and E2F transcription factor 3 (E2F3) were confirmed to be targets of miR-145. In addition, restoration of these 2 genes significantly reversed the tumor suppressive effects of miR-145. Collectively, the results indicated that miR-145 serves a critical role in suppressing the biological behavior of EOC cells by targeting CCND2 and E2F3. Therefore, miR-145 was suggested to be a potential miRNA-based therapeutic target in ovarian cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2019
31. Intracellular self-enhanced rolling circle amplification to image specific miRNAs within tumor cells.
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Chen, Yan-Ru, Han, Ying, Liu, Ran, Xue, Chang, Xu, Huo, Shen, Zhifa, and Wu, Zai-Sheng
- Subjects
- *
MICRORNA , *LIGASES , *HOMOLOGOUS chromosomes , *FLUORESCENCE in situ hybridization , *CANCER treatment - Abstract
Highlights • A sensitive self-enhanced rolling circle amplification strategy was proposed even if only two probes were involved. • A sensing platform is developed for intracellular miRNA imaging, displaying high sensitivity and desirable universality. • The measured data demonstrates its potential application in clinical diagnosis and other areas relying on miRNA analysis. Abstract MicroRNAs (miRs) are a class of non-coding, small RNA molecules that play important roles in gene expression. The aberrant expression of miRs is associated with various human diseases, and miRs have been regarded as biomarkers and therapeutic targets in cancer treatment. In this work, using miR-21 as model target species, an efficiently self-enhanced rolling circle amplification (seRCA)-based biosensing platform was developed for the ultrasensitive detection of cancer-related miRs. In the presence of target, a linear DNA template can be cyclized by ligase and initiate the first RCA (fRCA) reaction. Without any separation step and chemical modification, the fRCA products (fRCAp) are capable of activating the second exponential RCA and produce a much higher fluorescence signal, causing the self-enhancement effect of RCA reaction. Because two different signal amplification processes are introduced, there are two linear dynamic ranges together over 7 orders of magnitude. Target miR can be detected down to 1.0 fM with very high specificity, eliminating the interference from homologous miRs. If a fluorescently modified oligonucleotide probe is involved, the seRCA-based biosensing strategy is able to be employed for the intracellular imaging of cancer-related miR. Significantly, the comparative evaluation demonstrates that the proposed strategy exhibits the impressive capability to execute the miR imaging within cells higher than classical fluorescence in situ hybridization (FISH) method. The newly-developed powerful sensing strategy for the specific miR imaging would offer a unique opportunity to promote molecular biological research, early diagnosis and treatment of human cancers. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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32. Epstein-Barr virus microRNAs regulate B cell receptor signal transduction and lytic reactivation.
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Chen, Yan, Fachko, Devin, Ivanov, Nikita S., Skinner, Camille M., and Skalsky, Rebecca L.
- Subjects
- *
EPSTEIN-Barr virus , *B cell receptors , *CELLULAR signal transduction , *MICRORNA , *BIOINFORMATICS - Abstract
MicroRNAs (miRNAs) are post-transcriptional regulatory RNAs that can modulate cell signaling and play key roles in cell state transitions. Epstein-Barr virus (EBV) expresses >40 viral miRNAs that manipulate both viral and cellular gene expression patterns and contribute to reprogramming of the host environment during infection. Here, we identified a subset of EBV miRNAs that desensitize cells to B cell receptor (BCR) stimuli, and attenuate the downstream activation of NF-kappaB or AP1-dependent transcription. Bioinformatics and pathway analysis of Ago PAR-CLIP datasets identified multiple EBV miRNA targets related to BCR signal transduction, including GRB2, SOS1, MALT1, RAC1, and INPP5D, which we validated in reporter assays. BCR signaling is critical for B cell activation, proliferation, and differentiation, and for EBV, is linked to reactivation. In functional assays, we demonstrate that EBV miR-BHRF1-2-5p contributes to the growth of latently infected B cells through GRB2 regulation. We further determined that activities of EBV miR-BHRF1-2-5p, EBV miR-BART2-5p, and a cellular miRNA, miR-17-5p, directly regulate virus reactivation triggered by BCR engagement. Our findings provide mechanistic insight into some of the key miRNA interactions impacting the proliferation of latently infected B cells and importantly, governing the latent to lytic switch. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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33. miR‑199b‑5p inhibits triple negative breast cancer cell proliferation, migration and invasion by targeting DDR1.
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Wu, Anhao, Chen, Yan, Liu, Yang, Lai, Yafang, and Liu, Dequan
- Subjects
- *
MICRORNA , *TRIPLE-negative breast cancer , *CANCER cell proliferation , *PROTEIN-tyrosine kinases , *CANCER cell migration , *CANCER treatment , *THERAPEUTICS , *DISCOIDIN domain receptor 1 - Abstract
Triple negative breast cancer (TNBC) has received increasing attention from oncologists worldwide due to its poor prognosis and paucity of targeted therapies. MicroRNAs (miRs) are a group of small non‑coding RNAs that are responsible for the post‑transcriptional regulation of various target genes. The present study demonstrated that the expression of miR‑199b‑5p in breast cancer tissue was significantly reduced compared with that in normal breast tissues by reverse transcription‑quantitative polymerase chain reaction. In addition, western blot analysis and luciferase reporter assays revealed that miR‑199b‑5p in TNBC cells inhibited discoidin domain receptor tyrosine kinase 1 expression by directly targeting its 3'‑untranslated region. Furthermore, miR‑199b‑5p markedly suppressed the proliferation and invasion of TNBC cells, as demonstrated by using wound‑healing, migration, invasion and proliferation assays. Collectively, these results indicate that miR‑199b‑5p may be a novel alternative therapeutic target for TNBC. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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34. Knockdown of MiR-20a Enhances Sensitivity of Colorectal Cancer Cells to Cisplatin by Increasing ASK1 Expression.
- Author
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Zhang, Luyao, He, Liang, Zhang, Hua, and Chen, Yan
- Subjects
COLON cancer treatment ,MICRORNA ,CISPLATIN ,POLYMERASE chain reaction ,LUCIFERASES ,CELL lines - Abstract
Background/Aims: Platinum-based chemotherapy is one of the most important strategies for treatment of colorectal cancer. To improve the therapeutic efficiency, adjuvant drugs were sought to sensitize colorectal cancer cells to platinum-based agents such as cisplatin. As previous research has shown that miRNAs are associated with chemosensitivity, we aimed to alter miRNA regulation in colorectal cancer cells to increase their chemosensitivity.Methods: MTT assays were performed to determine the viability of HT29, SW480, and LoVo cells. Quantitative real time polymerase chain reaction (qRT-PCR) was performed to examine the expression of miR-20a in these cell lines. Regulation of the miR-20a/ASK1 axis was confirmed by western blotting and luciferase reporter assays. After treatment with miR-20a inhibitor (anti-miR-20a) and cisplatin, production of reactive oxygen species (ROS), mitochondrial membrane potential, and apoptosis were measured by flow cytometry. Activation of ASK1, Bcl-xl, JNK, and caspase-9, -7, and -3 was detected by western blotting.Results: miR-20a was overexpressed in colorectal cancer cell lines. Furthermore, knockdown of miR-20a increased the sensitivity of colorectal cancer cells to cisplatin treatment in vitro and in vivo. We demonstrated that the ASK1 gene was the target of miR-20a, and knockdown of miR-20a increased the expression of ASK1 in colorectal cancer cells. As cisplatin treatment induced production of ROS, knockdown of miR-20a enhanced ROS signaling through promoting the phosphorylation of ASK1. Phosphorylation of JNK and the subsequent mitochondrial apoptosis were triggered by the combination of cisplatin and anti-miR-20a.Conclusions: Knockdown of miR-20a enhanced sensitivity of colorectal cancer cells to cisplatin through the ROS/ASK1/JNK pathway. [ABSTRACT FROM AUTHOR]- Published
- 2018
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35. Tudor‑staphylococcal nuclease regulates the expression and biological function of alkylglycerone phosphate synthase via nuclear factor‑κB and microRNA‑127 in human glioma U87MG cells.
- Author
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Zhang, Yongqiang, Jia, Jun, Li, Ying, ChEN, Yan-Ge, Huang, Huan, Qiao, Yang, and Zhu, Yu
- Subjects
GLIOMAS ,NF-kappa B ,MICRORNA ,CANCER cell proliferation ,CANCER cell migration - Abstract
Glioma is one of the malignant tumor types detrimental to human health; therefore, it is important to find novel targets and therapeutics for this tumor. The downregulated expression of Tudor‑staphylococcal nuclease (SN) and alkylglycerone phosphate synthase (AGPS) can decrease cancer malignancy, and the overexpression of them can the increase viability and migration potential of various tumor cell types; however, the role of AGPS in the proliferation and migration of glioma, and the association of Tudor‑SN and AGPS in human glioma is not clear. In the present study, it was determined that AGPS silencing suppressed the proliferation and migration potential of glioma U87MG cells, and suppressed the expression of the circular RNAs circ‑ubiquitin‑associated protein 2, circ‑zinc finger protein 292 and circ‑homeodomain‑interacting protein kinase 3, and the long non‑coding RNAs H19 imprinted maternally expressed transcript (non‑protein coding), colon cancer‑associated transcript 1 (non‑protein coding) and hepatocellular carcinoma upregulated long non‑coding RNA. Furthermore, Tudor‑SN silencing suppressed the expression of AGPS; however, nuclear factor (NF)‑κB and microRNA (miR)‑127 retrieval experiments partially reduced the expression of AGPS. Additionally, it was determined that Tudor‑SN silencing suppressed the activity of the mechanistic target of rapamycin (mTOR) signaling pathway, and NF‑κB and miR‑127 retrieval experiments partially reduced the activity of mTOR. Therefore, it was considered that NF‑κB and miR‑127 may be the mediators of Tudor‑SN‑regulated AGPS via the mTOR signaling pathway. These results improve on our knowledge of the mechanisms underlying Tudor‑SN and AGPS in human glioma. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
36. Enhancing anti-tumor efficiency in hepatocellular carcinoma through the autophagy inhibition by miR-375/sorafenib in lipid-coated calcium carbonate nanoparticles.
- Author
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Zhao, Pengxuan, Li, Minsi, Wang, Yao, Chen, Yan, He, Chuanchuan, Zhang, Xiaojuan, Yang, Tan, Lu, Yao, You, Jia, Lee, Robert J., and Xiang, Guangya
- Subjects
ANTINEOPLASTIC agents ,LIVER cancer ,AUTOPHAGY ,MICRORNA ,SORAFENIB - Abstract
Sorafenib is a first-line drug for hepatocellular carcinoma (HCC). Autophagy has been shown to facilitate sorafenib resistance. miR-375 has been shown to be an inhibitor of autophagy. In this study, miR-375 and sorafenib were co-loaded into calcium carbonate nanoparticles with lipid coating (miR-375/Sf-LCC NPs). The nanoparticles had high loading efficiency and were ∼50 nm in diameter. Besides, the NPs could increase the stability and residence time of both drugs. Moreover, we demonstrated that autophagy was activated in HCC cells by sorafenib but not by miR-375/Sf-LCC NPs. In vitro , miR-375/Sf-LCC NPs exhibited pH-dependent drug release and potent cytotoxicity. In vivo , miR-375/Sf-LCC NPs increased miR-375 and sorafenib uptake in tumor (2 folds compared with Lipofectamine 2000-miR-375 and 2–5 folds compared with free sorafenib). Furthermore, miR-375/Sf-LCC NPs showed greatly enhanced therapeutic efficacy in an HCC xenograft model. These findings suggest that miR-375/Sf-LCC NPs may be a promising agent for the HCC therapy. Statement of Significance Hepatocellular carcinoma (HCC) is the most common primary liver tumor and the third leading cause of cancer mortality globally. In this manuscript, miR-375 and sorafenib were co-loaded into calcium carbonate nanoparticles with lipid coating (miR-375/Sf-LCC NPs) to treat HCC. We demonstrated that miR-375/Sf-LCC NPs can deliver sorafenib and miR-375 into HCC cells and tumor tissues, increase drug retention time in tumor, significantly inhibit autophagy and produce enhanced anti-tumor effect. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
37. MiRNA signature predicts the response of patients with advanced lung adenocarcinoma to platinum-based treatment.
- Author
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Xu, Xiaoyue, Yu, Shaorong, Sun, Wenbo, Qin, Xiaobing, Chen, Yan, Zhou, Leilei, Lou, Rui, Dong, Shuchen, Shen, Bo, Wu, Jianzhong, Zang, Jialan, Cao, Haixia, Shi, Meiqi, Zhang, Qin, and Feng, Jifeng
- Subjects
MICRORNA ,LUNG cancer ,ADENOCARCINOMA ,CANCER chemotherapy ,PLATINUM ,GENETICS ,THERAPEUTICS - Abstract
Background: Accumulating literature proved that miRNAs can regulate the sensitivity of platinum and act as a promising candidate to predict the response of patients with lung adenocarcinoma to chemotherapy. However, most studies on miRNAs were restricted to in vitro experiments. This study aimed to evaluate whether miRNAs alone or in combination (miRNA signature) can act as predictive biomarkers of platinum-based chemotherapy in patients with lung adenocarcinoma.Methods: Eight miRNAs that most probably predict the efficacy of platinum were screened in 111 tumor tissues of lung adenocarcinoma. Univariate and multivariate Cox analyses, Kaplan–Meier survival curve analysis, Chi-square test, and univariate and multivariate logistic regression analyses were employed to determine whether miRNA expression is associated with the response of patients to platinum-based chemotherapy. The maximum significant odds ratio value was acquired by multiple cycles of multivariate logistic regression analysis. The cut-off points of miRNAs were obtained. A miRNA chemo-sensibility index (CI) formula was established, and its prediction performance was confirmed in another independent set (
n = 31).Results: Underexpression of three miRNAs (miRNA-21, miRNA-125b, and miRNA-224) was independently associated with the chemotherapy sensitivity of patients with lung adenocarcinoma. The miRNA CI formula containing these three miRNAs was calculated as (1.364 × miR-21) + (1.323 × miR-125b) + (1.131 × miR-224). A high CI was related to platinum-based chemotherapy resistance, and its prediction performance was confirmed in the testing set. The MAPK, PI3K-Akt, Ras, and cGMP-PKG signaling pathways were considered to be most probably correlated with platinum resistance.Conclusion: Our miRNA CI formula can act as an independent predictor to predict the response of patients with lung adenocarcinoma to platinum-based chemotherapy. [ABSTRACT FROM AUTHOR]- Published
- 2018
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- View/download PDF
38. miR-34a is involved in CSE-induced apoptosis of human pulmonary microvascular endothelial cells by targeting Notch-1 receptor protein.
- Author
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Long, Ying-Jiao, Liu, Xiao-Peng, Chen, Shan-Shan, Zong, Dan-Dan, Chen, Yan, and Chen, Ping
- Subjects
OBSTRUCTIVE lung diseases ,MICRORNA ,APOPTOSIS ,ENDOTHELIAL cells ,GENE targeting ,NOTCH genes ,GENETICS - Abstract
Background: Abnormal apoptosis of lung endothelial cells has been observed in emphysematous lung tissue and has been suggested to be an important upstream event in the pathogenesis of chronic obstructive pulmonary disease (COPD). Studies have shown that microRNAs (miRNAs) contribute to the pathogenesis of pulmonary diseases by regulating cell apoptosis. The present study was designed to investigate the expression of microRNA-34a (miR-34a) in human pulmonary microvascular endothelial cells (HPMECs) exposed to cigarette smoke extract (CSE), and the potential regulatory role of miR-34a in endothelial cell apoptosis.Results: Our results showed that the expression of miR-34a was significantly increased in CSE-treated HPMECs, and inhibiting miR-34a attenuated CSE-induced HPMEC apoptosis. Furthermore, expression of Notch-1, a receptor protein in the Notch signalling pathway, was decreased and was inversely correlated with miR-34a expression in HPMECs treated with CSE. Computational miRNA target prediction confirmed that Notch-1 is a target of miR-34a. Luciferase reporter assay further confirmed the direct interaction between miR-34a and the 3'-untranslated region (UTR) of Notch-1. Restoration of Notch-1 pathway was able to partially block the effect of miR-34a on HPMEC apoptosis. These results indicate that Notch-1 is a critical downstream target of miR-34a in regulating the CSE-induced HPMEC apoptosis.Conclusions: Our results suggest that miR-34a plays a key role in CSE-induced endothelial cell apoptosis by directly regulating its target gene Notch-1 in endothelial cells. [ABSTRACT FROM AUTHOR]- Published
- 2018
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39. Nimodipine attenuates tau phosphorylation at Ser396 via miR-132/GSK-3β pathway in chronic cerebral hypoperfusion rats.
- Author
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Tan, Zihu, Chen, Yan, Xie, Wenting, Liu, Xi, Zhu, Yuanyue, and Zhu, Yan
- Subjects
- *
NEUROLOGICAL disorders , *THERAPEUTICS , *NIMODIPINE , *NEUROPROTECTIVE agents , *MICRORNA , *PHOSPHORYLATION - Abstract
Chronic cerebral hypofusion (CCH) promotes hyperphosphorylation of tau proteins, a key neuropathological trait that reflects neurodegenerative disorders. Nimodipine, an L-type calcium channel antagonist, has been reported to show neuroprotective effects. In this study, we investigated the potential mechanism of nimodipine in tauopathies induced by CCH. MiR-132 is downregulated in tauopathies such as AD and directly targets tau mRNA to regulate its expression. Here, we report that CCH induced miR-132 deficiency and increased tau phosphorylation at Ser396 while tau expression was not influenced. Nimodipine treatment attenuated CCH induced tau phosphorylation by up-regulating expression of miR-132. Furthermore, nimodipine inhibited activation of GSK-3β and neuronal apoptosis induced by CCH. Interestingly, GSK-3βmRNA level negatively correlated with the expression of miR-132. These findings support a role for nimodipine inhibiting tau phosphorylation at Ser396 via miR-132/GSK-3β. Therefore, nimodipine may be a candidate for the treatment of tauopathy present in CCH. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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- View/download PDF
40. Abnormally expressed microRNA as auxiliary biomarkers for nasopharyngeal carcinoma: A meta-analysis.
- Author
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Xiao, Zhenzhou, Peng, Wei, Zhou, Xusheng, Luo, Xiaoli, Chen, Yan, and Cui, Zhaolei
- Subjects
META-analysis ,MICRORNA ,CANCER diagnosis ,NON-coding RNA - Abstract
Aberrant expression of microRNA (miRNA) has been highlighted as a helpful indicator to aid in nasopharyngeal carcinoma (NPC) diagnosis. The present meta-analysis aimed to validate the efficacy of miRNA as potential biomarkers for NPC detection. Publication searches were conducted on the online PubMed and EMBASE databases from inception to June 2016. A bivariate meta-analysis was performed to generate the diagnostic parameters based on Meta-Disc 1.4 and Stata 12.0 programs. Sensitivity analysis and meta-regression tests were applied to trace heterogeneity sources among eligible studies. A total of six studies comprising 528 patients with NPC and 252 matched controls were enrolled. Results from the present meta-analysis demonstrated that miRNA testing achieved a pooled sensitivity of 0.78 [95% confidence interval (CI), 0.70-0.84] and specificity of 0.79 (95% CI, 0.73-0.84) in confirming NPC, corresponding to an area under the curve (AUC) value of 0.85. Additionally, the pooled diagnostic odds ratio was estimated to be 9.01 (95% CI, 5.62-14.44), along with a positive likelihood ratio of 2.81 (95% CI, 2.19-3.61) and negative likelihood ratio of 0.35 (95% CI, 0.28-0.44). Additionally, the stratified analyses revealed that paralleled testing of miRNA sustained a pooled accuracy superior compared with that of single miRNA testing (sensitivity, 0.88 vs. 0.70; specificity, 0.85 vs. 0.69; AUC, 0.95 vs. 0.75). Testing of miRNA harbors a moderate diagnostic efficacy and is acceptable as an auxiliary biomarker for NPC diagnosis. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
41. MiR-375 delivered by lipid-coated doxorubicin-calcium carbonate nanoparticles overcomes chemoresistance in hepatocellular carcinoma.
- Author
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Zhao, Pengxuan, Wu, Shuangping, Cheng, Yao, You, Jia, Chen, Yan, Li, Minsi, He, Chuanchuan, Zhang, Xiaojuan, Yang, Tan, Lu, Yao, Lee, Robert J., He, Xingxing, and Xiang, Guangya
- Subjects
DRUG delivery systems ,MICRORNA ,DOXORUBICIN ,DRUG coatings ,NANOMEDICINE ,CALCIUM carbonate ,LIVER cancer - Abstract
Hepatocellular carcinoma (HCC) is a prevalent and lethal disease that is characterized by drug resistance. Doxorubicin (DOX) is a widely used chemotherapeutic drug and miR-375 has been shown to be a tumor suppressor in HCC. Here, we reported that miR-375 and DOX co-loaded into lipid-coated calcium carbonate nanoparticles (LCC-DOX/miR-375 NPs), enhanced the anti-tumor effects through combination therapy, and were highly effective in reversing drug resistance in HCC. LCC-DOX/miR-375 NPs were prepared by a reverse microemulsions method. In vitro , LCC-DOX/miR-375 NPs exhibited enhanced intracellular accumulation, pH-sensitive DOX release and potent cytotoxicity. In vivo , LCC-DOX/miR-375 NPs showed efficient antitumor effect both in xenograft and primary HCC murine models. Our results showed that the LCC-DOX/miR-375 nanoparticles provide a novel strategy to overcome the drug resistance and promote addictive effect between miR-375 and DOX in HCC. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
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42. Protective Effects of MicroRNA-126 on Human Cardiac Microvascular Endothelial Cells Against Hypoxia/Reoxygenation-Induced Injury and Inflammatory Response by Activating PI3K/Akt/eNOS Signaling Pathway.
- Author
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Yang, Hong-Hui, Chen, Yan, Gao, Chuan-Yu, Cui, Zhen-Tian, and Yao, Jian-Min
- Subjects
- *
MICRORNA , *HYPOXEMIA , *HEART cells , *CELLULAR signal transduction , *SUPEROXIDE dismutase , *INFLAMMATION , *ENZYME-linked immunosorbent assay , *VASCULAR endothelial growth factors , *PHYSIOLOGY , *THERAPEUTICS - Abstract
Objective: This study explored the protective effects of the microRNA-126 (miR-126)- mediated PI3K/Akt/eNOS signaling pathway on human cardiac microvascular endothelial cells (HCMECs) against hypoxia/reoxygenation (H/R)-induced injury and the inflammatory response. Methods: Untreated HCMECs were selected for the control group. After H/R treatment and cell transfection, the HCMECs were assigned to the H/R, miR-126 mimic, mimicnegative control (NC), miR-126 inhibitor, inhibitor-NC, wortmannin (an inhibitor of PI3K) and miR-126 mimic + wortmannin groups. Super oxide dismutase (SOD), nitric oxide (NO), vascular endothelial growth factor (VEGF) and reactive oxygen species (ROS) were measured utilizing commercial kits. Quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were performed to detect miR-126 expression and the mRNA and protein expression of inflammatory factors. Western blotting was used to determine the expression of key members in the PI3K/Akt/eNOS signaling pathway. ACCK- 8 assay and flow cytometry were employed to examine cell proliferation and apoptosis, respectively. The angiogenic ability in each group was detected by the lumen formation test. Results: Compared to the control group, p/t-PI3K, p/t-Akt and p/t-eNOS expression, NO, VEGF and SOD levels, cell proliferation and in vitro lumen formation ability were decreased, while the ROS content, interleukin (IL)-6, IL-10 and tumor necrosis factor (TNF)-α expression and cell apoptosis were significantly increased in the H/R, mimic-NC, miR-126 inhibitor, inhibitor- NC, wortmannin and miR-126 mimic + wortmannin groups. Additionally, in comparison with the H/R group, the miR-126 mimic group had elevated p/t-PI3K, p/t-Akt and p/t-eNOS expression, increased NO, VEGF and SOD contents, and strengthened cell proliferation and lumen formation abilities but also exhibited decreased ROS content, reduced IL-6, IL-10 and TNF-α expressions, and weakened cell apoptosis, while the miR-126 inhibitor and wortmannin group exhibited the opposite results. Furthermore, decreased p/t-PI3K, p/t-Akt and p/t-eNOS expressions, decreased NO, VEGF and SOD contents, cell proliferation and lumen formation abilities, as well as increased ROS content, increased IL-6, IL-10 and TNF-α expression, and increased cell apoptosis were observed in the miR-126 mimic + wortmannin group compared to themiR-126 mimic group. Conclusions: These findings indicated that miR-126 protects HCMECs from H/R-induced injury and inflammatory response by activating the PI3K/Akt/ eNOS signaling pathway. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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43. TargetLink, a new method for identifying the endogenous target set of a specific microRNA in intact living cells.
- Author
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Xu, Yan, Chen, Yan, Li, Daliang, Liu, Qing, Xuan, Zhenyu, and Li, Wen-Hong
- Abstract
MicroRNAs are small non-coding RNAs acting as posttranscriptional repressors of gene expression. Identifying mRNA targets of a given miRNA remains an outstanding challenge in the field. We have developed a new experimental approach, TargetLink, that applied locked nucleic acid (LNA) as the affinity probe to enrich target genes of a specific microRNA in intact cells. TargetLink also consists a rigorous and systematic data analysis pipeline to identify target genes by comparing LNA-enriched sequences between experimental and control samples. Using miR-21 as a test microRNA, we identified 12 target genes of miR-21 in a human colorectal cancer cell by this approach. The majority of the identified targets interacted with miR-21 via imperfect seed pairing. Target validation confirmed that miR-21 repressed the expression of the identified targets. The cellular abundance of the identified miR-21 target transcripts varied over a wide range, with some targets expressed at a rather low level, confirming that both abundant and rare transcripts are susceptible to regulation by microRNAs, and that TargetLink is an efficient approach for identifying the target set of a specific microRNA in intact cells. C20orf111, one of the novel targets identified by TargetLink, was found to reside in the nuclear speckle and to be reliably repressed by miR-21 through the interaction at its coding sequence. [ABSTRACT FROM PUBLISHER]
- Published
- 2017
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44. A novel serum microRNA signature to screen esophageal squamous cell carcinoma.
- Author
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Huang, Zebo, Zhang, Lan, Zhu, Danxia, Shan, Xia, Zhou, Xin, Qi, Lian‐wen, Wu, Lirong, Zhu, Jun, Cheng, Wenfang, Zhang, Huo, Chen, Yan, Zhu, Wei, Wang, Tongshan, and Liu, Ping
- Subjects
MICRORNA ,DIAGNOSIS of esophageal cancer ,SQUAMOUS cell carcinoma ,BIOMARKERS ,REVERSE transcriptase polymerase chain reaction ,EXOSOMES - Abstract
Circulating microRNAs (miRNAs) have been used as promising diagnostic biomarkers for esophageal squamous cell carcinoma (ESCC). We performed miRNA expression profiling using quantitative reverse transcription polymerase chain reaction (qRT-PCR) based Exiqon panels from three ESCC pools and one normal control (NC) pool samples. Using qRT-PCR, identified serum miRNAs were further confirmed in training (32 ESCC vs. 32 NCs) and testing stages (108 ESCC vs. 96 NCs). Consequently, five serum miRNAs (miR-20b-5p, miR-28-3p, miR-192-5p, miR-223-3p, and miR-296-5p) were significantly overexpressed in ESCC compared with NCs. The diagnostic value of the 5-miRNA signature was validated by an external cohort (60 ESCC vs. 60 NCs). The areas under the receiver operating characteristic curve (ROC) of the 5-miRNA signature were 0.753, 0.763, and 0.966 for the training, testing, and the external validation stages, respectively. The expression levels of the miRNAs were also determined in tissues, arterial serum, and exosomes. MiR-20b-5p, miR-28-3p, and miR-192-5p were significantly upregulated in ESCC tissues, while miR-296-5p was overexpressed in ESCC serum exosomes. In conclusion, we identified a 5-miRNA signature in serum for the detection of ESCC. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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- View/download PDF
45. MicroRNA-18a modulates P53 expression by targeting IRF2 in gastric cancer patients.
- Author
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Chen, Yan‐Jie, Wu, Hao, Zhu, Ji‐Min, Li, Xiao‐Dan, Luo, Si‐Wei, Dong, Ling, Liu, Tao‐Tao, and Shen, Xi‐Zhong
- Subjects
- *
MICRORNA , *CANCER patients , *ONCOLOGY , *CARCINOGENS , *TUMORS - Abstract
Background and Aim: MicroRNA-18a (miR-18a) has been reported to be upregulated in gastric cancer (GC) tissues compared with normal gastric tissues. However, little is known about its prognostic value and biological roles. Methods: In this study, miR-18a expression in gastric adenocarcinoma (GAC) tissues and adjacent non-tumor tissues was validated by in situ hybridization, and the predictive values of miR-18a were explored. The biological roles of miR-18a and the underlying signal pathway were investigated in GC cell lines. Results: Overexpressed intra-tumoral miR-18a was associated with poor survival rate and was an independent prognostic factor for overall survival rate ( P < 0.001) in GC patients. Forced expression of miR-18a remarkably enhanced cell proliferation, migration, and invasion in GC cells, while inhibition of miR-18a caused the opposite effects. Further study showed that miR-18a suppressed the expression of interferon regulatory factor 2 (IRF2) by directly binding to its 3′-untranslated region. Moreover, miR-18a expression levels are inversely correlated with IRF2 in human GC tissues. Western blot showed that forced expression of miR-18a could not only downregulate the expression of IRF2, but also inhibit the expression of P53, suggesting that IRF2 might play as a tumor suppressor by regulating P53 signaling in GC. Conclusion: miR-18a modulated P53 expression by directly targeting IRF2 and had a high predictive value for prognosis of GAC patients. These results may lead to identification of therapeutic candidates of GC. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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- View/download PDF
46. The miR-134 attenuates the expression of transcription factor FOXM1 during pluripotent NT2/D1 embryonal carcinoma cell differentiation.
- Author
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Chen, Yan, Meng, Lei, Yu, Qiqi, Dong, Difei, Tan, Guixiang, Huang, Xiaoqin, and Tan, Yongjun
- Subjects
- *
MICRORNA , *GENE expression , *FORKHEAD transcription factors , *PLURIPOTENT stem cells , *EMBRYONAL tumors , *CANCER cell differentiation , *LABORATORY mice - Abstract
Transcription factor FOXM1 plays a critical role in maintenance of stem cell pluripotency through stimulating the transcription of pluripotency-related genes in mouse pluripotent stem cells. In this study, we have found that the repression of FOXM1 expression is mediated by FOXM1 3′UTR during retinoic acid-induced differentiation of human pluripotent NT2/D1 embryonal carcinoma cells. FOXM1 3′UTR contains a microRNA response element (MRE) for miR-134, which has been shown to attenuate the expression of pluripotency-related genes post-transcriptionally during mouse embryonic stem cell differentiation. We have determined that miR-134 is induced during RA-induced differentiation of NT2/D1 cells and the overexpression of miR-134 represses the expression of FOXM1 protein but not FOXM1 mRNA. Furthermore, the expression of OCT4 is diminished by FOXM1 knockdown and the OCT4 promoter is regulated directly by FOXM1, suggesting that FOXM1 is required for maintaining the expression of OCT4 in NT2/D1 cells. Together, our results suggest that FOXM1 is essential for human pluripotent stem cells and miR-134 attenuates its expression during differentiation. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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- View/download PDF
47. Circulating microRNAs as a Fingerprint for Endometrial Endometrioid Adenocarcinoma.
- Author
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Wang, Lin, Chen, Yan-Jie, Xu, Kai, Xu, Hua, Shen, Xi-Zhong, and Tu, Rui-Qin
- Subjects
- *
MICRORNA , *CASE-control method , *ENDOMETRIAL cancer , *BIOMARKERS , *REVERSE transcriptase polymerase chain reaction , *LOGISTIC regression analysis - Abstract
Background: Endometrial cancer is the most common malignancy of the female genital tract worldwide, and endometrial endometrioid adenocarcinoma (EEC) is the major histological type of endometrial cancer. There is a great need for better markers with high sensitivity and specificity to permit early diagnosis and proper management of EEC. The aim of our study is to identify a miRNA classifier within plasma as a noninvasive biomarker for EEC diagnosis. Methods: This study was a retrospective case-control analysis which contained two independent cohorts including 93 participants. First, we screened 375 miRNAs in 29 plasma samples. 9 of the miRNAs were selected to be evaluated their expression by quantitative reverse-transcriptase polymerase chain reaction. A stepwise logistic regression model was then used to establish a new classifier in the validation cohort. Area under the receiver operating characteristic curve was used to evaluate the diagnostic accuracy. Co-expression analysis was used to verify the independence of results. Results: miR-15b, -27a, and -223 were found to be differentially expressed in the EEC plasma between the two cohorts and had few connections with other miRNAs. The areas under the curve (AUC) were 0.768, 0.813, and 0.768 for miR-15b, -27a, and 223, respectively. miR-27a and CA125 can be combined as a potential non-invasive biomarker for detecting EEC, with the AUC of 0.894. Conclusion: Our study demonstrated three miRNAs, including miR-15b, -27a, and -233 have a good clinical value in EEC diagnosis. The classifier, including miR-27a and CA125, demonstrated a high accuracy in the diagnosis of EEC and might serve as a novel non-invasive biomarker in the future. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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- View/download PDF
48. Knocking down CDK4 mediates the elevation of let-7c suppressing cell growth in nasopharyngeal carcinoma.
- Author
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Zhen Liu, Xiaobin Long, Cheng Chao, Chen Yan, Qiangyun Wu, Shengni Hua, Yajie Zhang, Aibing Wu, and Weiyi Fang
- Subjects
NASOPHARYNX cancer ,CYCLIN-dependent kinases ,GROWTH factors ,GENE expression ,MICRORNA ,IMMUNOHISTOCHEMISTRY - Abstract
Background CDK4 is a protein kinase in the CDK family important for G1/S phase cell cycle progression. However, the roles and molecular mechanisms of CDK4 triggering nasopharynx carcinogenesis are still unclear. Methods Lentiviral-vector mediated shRNA was used to suppress CDK4 expression and examine its molecular mechanisms. Using immunohistochemistry, we analyzed CDK4 protein expression in clinicopathologically characterized nasopharyngeal carcinoma (NPC) cases and nasopharyngeal tissues (NPs). Survival curves were plotted by the Kaplan-Meier method and compared using the log-rank test. Results In this investigation, we knocked down CDK4 expression and observed that NPC cell growth and cell cycle progression were significantly blocked by suppressing expression of CCND1, CDK6, and E2F1 as well as elevated p21 expression. Further, we found that reduced CDK4 expression elevated the expression of let-7c, a tumor-suppressive miRNA modulated by E2F1. We found that let-7c was markedly downregulated in NPC tissues compared to NPs and suppressed cell growth and cell cycle progression by modulating p15/p16/CDK4/E2F1 pathway. Finally, CDK4 protein was observed to be overexpressed in NPC tissues and could be considered an unfavorable prognosis factor for NPC patients although its independent prognostic value did not reach statistical significance (p = 0.087). Conclusions Our results demonstrated that overexpressed CDK4 is an unfavorable prognostic factor which suppresses the expression of tumor suppressive-factor let-7c through p21/CCND1/CDK6/E2F1 signaling, and inhibits cell proliferation by p15/p16/CDK4/E2F1 feedback signaling in NPC. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
49. Serum miR-210 and miR-30a expressions tend to revert to fetal levels in Chinese adult patients with chronic heart failure.
- Author
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Zhao, Dong-Sheng, Chen, Yan, Jiang, Hui, Lu, Jing-Ping, Zhang, Gang, Geng, Jie, Zhang, Qing, Shen, Jian-Hua, Zhou, Xin, Zhu, Wei, and Shan, Qi-Jun
- Subjects
- *
BLOOD serum analysis , *MICRORNA , *GENE expression , *EMERGENCY medical services , *BLOOD plasma , *INTERNAL medicine - Abstract
Abstract: Background: MicroRNAs (miRNAs) are widely involved in the process of chronic heart failure (HF), which is characterized by reactivation of the fetal gene program. Here, we examined whether the serum expression levels of some HF-related miRNAs in adult HF patients would tend to revert to fetal levels. Methods and results: Serum was obtained from the peripheral venous blood of 22 HF patients, 18 asymptomatic controls, and the umbilical venous blood of 9 fetuses from 9 independent parturitions. Serum pools of the three groups were initially screened against 40 known HF-associated miRNAs via quantitative reverse transcriptase polymerase chain reaction. Twenty-seven miRNAs were stably expressed in the serum pools. Nine miRNAs showed similar expression levels in the HF and fetus groups compared to the controls, two of which (miR-210, miR-30a) were significantly up-regulated in both groups. These miRNAs showed high diagnostic accuracy and correlations with blood N-terminal prohormone of brain natriuretic peptide, identifying them as potential biomarkers for HF. Putative targets of the miRNAs were predicted with online software programs, and the Kyoto Encyclopedia of Genes and Genomes pathway analysis was employed to identify miRNA-regulated functional modules. In particular, miR-210 seemed to be more closely related than miR-30a to the pathological mechanisms of HF, including the calcium signaling, vascular smooth muscle contraction, transforming growth factor-β signaling, and aldosterone-regulated sodium reabsorption pathways. Conclusion: The serum expression levels of some HF-related miRNAs in HF patients tended towards fetal levels. Among them, miR-210 and miR-30a were elevated in the HF and fetus groups. [Copyright &y& Elsevier]
- Published
- 2013
- Full Text
- View/download PDF
50. Circulating microRNAs as a Fingerprint for Liver Cirrhosis.
- Author
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Chen, Yan-Jie, Zhu, Ji-Min, Wu, Hao, Fan, Jia, Zhou, Jian, Hu, Jie, Yu, Qian, Liu, Tao-Tao, Yang, Lei, Wu, Chun-Lei, Guo, Xiao-Ling, Huang, Xiao-Wu, and Shen, Xi-Zhong
- Subjects
- *
MICRORNA , *HUMAN fingerprints , *CIRRHOSIS of the liver , *BIOMARKERS , *GASTROENTEROLOGY , *HEPATOLOGY , *HEPATITIS B - Abstract
Background: Sensitive and specific detection of liver cirrhosis is an urgent need for optimal individualized management of disease activity. Substantial studies have identified circulation miRNAs as biomarkers for diverse diseases including chronic liver diseases. In this study, we investigated the plasma miRNA signature to serve as a potential diagnostic biomarker for silent liver cirrhosis. Methods: A genome-wide miRNA microarray was first performed in 80 plasma specimens. Six candidate miRNAs were selected and then trained in CHB-related cirrhosis and controls by qPCR. A classifier, miR-106b and miR-181b, was validated finally in two independent cohorts including CHB-related silent cirrhosis and controls, as well as non−CHB-related cirrhosis and controls as validation sets, respectively. Results: A profile of 2 miRNAs (miR-106b and miR-181b) was identified as liver cirrhosis biomarkers irrespective of etiology. The classifier constructed by the two miRNAs provided a high diagnostic accuracy for cirrhosis (AUC = 0.882 for CHB-related cirrhosis in the training set, 0.774 for CHB-related silent cirrhosis in one validation set, and 0.915 for non−CHB-related cirrhosis in another validation set). Conclusion: Our study demonstrated that the combined detection of miR-106b and miR-181b has a considerable clinical value to diagnose patients with liver cirrhosis, especially those at early stage. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
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