31 results on '"Xince Huang"'
Search Results
2. Circular RNA circERBB2 promotes gallbladder cancer progression by regulating PA2G4-dependent rDNA transcription
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Xince Huang, Ming He, Shuai Huang, Ruirong Lin, Ming Zhan, Dong Yang, Hui Shen, Sunwang Xu, Wei Cheng, Jianxiu Yu, Zilong Qiu, and Jian Wang
- Subjects
Circular RNA ,circERBB2 ,Gallbladder cancer ,rDNA ,PA2G4 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background CircRNAs are found to affect initiation and progression of several cancer types. However, whether circRNAs are implicated in gallbladder cancer (GBC) progression remains obscure. Methods We perform RNA sequencing in 10 pairs of GBC and para-cancer tissues. CCK8 and clone formation assays are used to evaluate proliferation ability of GBC cells. qPCR and Western blot are used to determine expression of RNAs and proteins, respectively. CircRNA-protein interaction is confirmed by RNA pulldown, RNA immunoprecipitation, and fluorescence in situ hybridization. Results We find that circRNA expression pattern is tremendously changed during GBC development. Among dozens of significantly changed circRNAs, a circRNA generated from the oncogene ERBB2, named as circERBB2, is one of the most significant changes. CircERBB2 promotes GBC proliferation, in vitro and in vivo. Other than being a miRNA sponge, circERBB2 accumulates in the nucleoli and regulates ribosomal DNA transcription, which is one of the rate-limiting steps of ribosome synthesis and cellular proliferation. CircERBB2 regulates nucleolar localization of PA2G4, thereby forming a circERBB2-PA2G4-TIFIA regulatory axis to modulate ribosomal DNA transcription and GBC proliferation. Increased expression of circERBB2 is associated with worse prognosis of GBC patients. Conclusions Our findings demonstrate that circERBB2 serves as an important regulator of cancer cell proliferation and shows the potential to be a new therapeutic target of GBC.
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- 2019
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- View/download PDF
3. PLEK2 promotes gallbladder cancer invasion and metastasis through EGFR/CCL2 pathway
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Hui Shen, Min He, Ruirong Lin, Ming Zhan, Sunwang Xu, Xince Huang, Chu Xu, Wei Chen, Yanhua Yao, Man Mohan, and Jian Wang
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PLEK2 ,EGFR ,CCL2 ,Metastasis ,Gallbladder Cancer ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Gallbladder cancer (GBC) is an extremely malignant tumor with a high mortality rate. Little is known about its invasion and metastasis mechanism so far. Methods To identify the driver genes in GBC metastasis, we performed a mRNA microarray of metastatic GBC and paired non-tumor samples, and found PLEK2 was markedly upregulated in GBC tissues. Next, the expression of PLEK2 in GBC were examined in a larger cohort of patients by qRT-PCR, western blot and IHC staining. The clinicopathologic correlation of PLEK2 was determined by statistical analyses. The biological involvement of PLEK2 in GBC metastasis and the underlying mechanisms were investigated. Results In this study, we found that PLEK2 had higher expression in GBC tumor tissues compared to non-cancerous adjacent tissues and cholecystolithiasis tissues. The clinicopathologic analyses showed PLEK2 expression was positively correlated with tumor TNM stage, distant metastasis and PLEK2 was an independent predictor of overall survival (OS) in GBC patients. The cellular function assays showed PLEK2 promoted GBC cells migration, invasion and liver metastasis in mouse model via the regulation of epithelial-mesenchymal transition (EMT) process. Our mass spectrum and co-immunoprecipitation (co-IP) assays demonstrated that PLEK2 could interact with the kinase domain of EGFR and suppress EGFR ubiquitination mediated by c-CBL, leading to constitutive activation of EGFR signaling. Furthermore, RNA-sequencing and qRT-PCR results demonstrated chemokine (C-C motif) ligand 2 (CCL2), a target gene downstream of PLEK2/EGFR signaling, mediated the motility-promoting function of PLEK2. Conclusions On the basis of these collective data, we propose that PLEK2 promotes the invasion and metastasis of GBC by EGFR/CCL2 pathway and PLEK2 can serve as a potential therapeutic target for GBC treatment.
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- 2019
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- View/download PDF
4. Correction to: Circular RNA circERBB2 promotes gallbladder cancer progression by regulating PA2G4-dependent rDNA transcription
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Xince Huang, Min He, Shuai Huang, Ruirong Lin, Ming Zhan, Dong Yang, Hui Shen, Sunwang Xu, Wei Cheng, Jianxiu Yu, Zilong Qiu, and Jian Wang
- Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2022
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5. Reduced Pancreatic Exocrine Function and Organellar Disarray in a Canine Model of Acute Pancreatitis.
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Yuepeng Jin, Yongyu Bai, Qiang Li, Pravin Avinash Bhugul, Xince Huang, Lewei Liu, Liangliang Pan, Haizhen Ni, Bicheng Chen, Hongwei Sun, Qiyu Zhang, Michael Hehir, and Mengtao Zhou
- Subjects
Medicine ,Science - Abstract
The aim of the present study was to investigate the pancreatic exocrine function in a canine model and to analyze the changes in organelles of pancreatic acinar cells during the early stage of acute pancreatitis (AP). AP was induced by retrograde injection of 5% sodium taurocholate (0.5 ml/kg) into the main pancreatic duct of dogs. The induction of AP resulted in serum hyperamylasemia and a marked reduction of amylase activity in the pancreatic fluid (PF). The pancreatic exocrine function was markedly decreased in subjects with AP compared with the control group. After the induction of AP, histological examination showed acinar cell edema, cytoplasmic vacuolization, fibroblasts infiltration, and inflammatory cell infiltration in the interstitium. Electron micrographs after the induction of AP revealed that most of the rough endoplasmic reticulum (RER) were dilated and that some of the ribosomes were no longer located on the RER. The mitochondria were swollen, with shortened and broken cristae. The present study demonstrated, in a canine model, a reduced volume of PF secretion with decreased enzyme secretion during the early stage of AP. Injury of mitochondria and dilatation and degranulation of RER may be responsible for the reduced exocrine function in AP. Furthermore, the present model and results may be useful for researching novel therapeutic measures in AP.
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- 2016
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6. Deoxycholic acid modulates the progression of gallbladder cancer through N6-methyladenosine-dependent microRNA maturation
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Weijian Li, Shuai Huang, Jianxiu Yu, Qiang Liu, Hui Wang, Wei Chen, Linhua Yang, Sunwang Xu, Zijie Zhang, Jian Wang, Hui Shen, Yongsheng Shi, Ming Zhan, Ruirong Lin, and Xince Huang
- Subjects
0301 basic medicine ,Cancer Research ,Cell signaling ,Akt/PKB signaling pathway ,Deoxycholic acid ,Biology ,medicine.disease ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,0302 clinical medicine ,chemistry ,Tumor progression ,030220 oncology & carcinogenesis ,microRNA ,Genetics ,medicine ,Cancer research ,Tensin ,Gallbladder cancer ,Molecular Biology ,PI3K/AKT/mTOR pathway - Abstract
Bile acids (BAs), well-defined signaling molecules with diverse metabolic functions, play important roles in cellular processes associated with many cancers. As one of the most common BAs, deoxycholic acid (DCA) is originally synthesized in the liver, stored in the gallbladder, and processed in the gut. DCA plays crucial roles in various tumors; however, functions and molecular mechanisms of DCA in gallbladder cancer (GBC) still remain poorly characterized. Here, we analyzed human GBC samples and found that DCA was significantly downregulated in GBC, and reduced levels of DCA was associated with poor clinical outcome in patients with GBC. DCA treatment impeded tumor progression by halting cell proliferation. DCA decreased miR-92b-3p expression in an m6A-dependent posttranscriptional modification manner by facilitating dissociation of METTL3 from METTL3–METTL14–WTAP complex, which increased the protein level of the phosphatase and tensin homolog, a newly identified target of miR-92b-3p, and subsequently inactivated the PI3K/AKT signaling pathway. Our findings revealed that DCA might function as a tumor suppressive factor in GBC at least by interfering with miR-92b-3p maturation, and suggested that DCA treatment could provide a new therapeutic strategy for GBC.
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- 2020
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7. Genome-wide CRISPR screen identifies ELP5 as a determinant of gemcitabine sensitivity in gallbladder cancer
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Qiang Liu, Jian Wang, Yongheng Shi, Wei Chen, Sunwang Xu, Xince Huang, Ruirong Lin, Man Mohan, Ming Zhan, Min He, Linhua Yang, Cen Jiang, Hui Shen, and Shuai Huang
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0301 basic medicine ,Male ,General Physics and Astronomy ,Apoptosis ,Deoxycytidine ,Heterogeneous-Nuclear Ribonucleoproteins ,Cohort Studies ,0302 clinical medicine ,RNA, Transfer ,CRISPR ,Clustered Regularly Interspaced Short Palindromic Repeats ,RNA Processing, Post-Transcriptional ,lcsh:Science ,Aged, 80 and over ,Multidisciplinary ,Translation (biology) ,Middle Aged ,030220 oncology & carcinogenesis ,Female ,Gallbladder Neoplasms ,medicine.drug ,Cell death ,Adult ,TRNA modification ,Antimetabolites, Antineoplastic ,Science ,Biology ,Internal Ribosome Entry Sites ,General Biochemistry, Genetics and Molecular Biology ,Article ,03 medical and health sciences ,Gastrointestinal cancer ,medicine ,Humans ,Gallbladder cancer ,Aged ,RNA ,General Chemistry ,medicine.disease ,Gemcitabine ,Internal ribosome entry site ,030104 developmental biology ,Cancer research ,lcsh:Q ,Tumor Suppressor Protein p53 ,Carrier Proteins ,Genome-Wide Association Study - Abstract
Gemcitabine is the first-line treatment for locally advanced and metastatic gallbladder cancer (GBC), but poor gemcitabine response is universal. Here, we utilize a genome-wide CRISPR screen to identify that loss of ELP5 reduces the gemcitabine-induced apoptosis in GBC cells in a P53-dependent manner through the Elongator complex and other uridine 34 (U34) tRNA-modifying enzymes. Mechanistically, loss of ELP5 impairs the integrity and stability of the Elongator complex to abrogate wobble U34 tRNA modification, and directly impedes the wobble U34 modification-dependent translation of hnRNPQ mRNA, a validated P53 internal ribosomal entry site (IRES) trans-acting factor. Downregulated hnRNPQ is unable to drive P53 IRES-dependent translation, but rescuing a U34 modification-independent hnRNPQ mutant could restore P53 translation and gemcitabine sensitivity in ELP5-depleted GBC cells. GBC patients with lower ELP5, hnRNPQ, or P53 expression have poor survival outcomes after gemcitabine chemotherapy. These results indicate that the Elongator/hnRNPQ/P53 axis controls gemcitabine sensitivity in GBC cells., Gemcitabine is used to treat gallbaldder cancer but patient responses are variable. Here, the authors use a genome-wide CRISPR screen and identify the translational elongator protein ELP5 as a protein that is important for mediating gemcitabine-induced apoptosis.
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- 2019
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8. Tamoxifen inhibits cell proliferation by impaired glucose metabolism in gallbladder cancer
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Wei Chen, Ming Zhan, Xince Huang, Sunwang Xu, Jian Wang, Ruirong Lin, Hui Shen, Hui Wang, and Shuai Huang
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0301 basic medicine ,AMPK ,Male ,Carcinogenesis ,Apoptosis ,medicine.disease_cause ,gallbladder cancer ,0302 clinical medicine ,Cytochrome P-450 Enzyme System ,Medicine ,Molecular Targeted Therapy ,skin and connective tissue diseases ,tamoxifen ,chemoresistance ,ROS ,glycolysis ,Middle Aged ,Prognosis ,Tumor Burden ,030220 oncology & carcinogenesis ,Molecular Medicine ,Hormonal therapy ,Immunohistochemistry ,Original Article ,Female ,Gallbladder Neoplasms ,medicine.drug ,Signal Transduction ,Cell Survival ,NF-E2-Related Factor 2 ,Ovariectomy ,Models, Biological ,03 medical and health sciences ,In vivo ,Cell Line, Tumor ,Humans ,Gallbladder cancer ,Aged ,Cell Proliferation ,Cisplatin ,business.industry ,Cell growth ,Adenylate Kinase ,Estrogen Receptor alpha ,Cell Biology ,Original Articles ,medicine.disease ,Xenograft Model Antitumor Assays ,030104 developmental biology ,Glucose ,Multivariate Analysis ,Cancer research ,business ,Reactive Oxygen Species ,Tamoxifen - Abstract
Gallbladder cancer (GBC) is the leading malignancy of biliary system showing refractory chemoresistance to current first‐line drugs. Growing epidemiological evidences have established that the incidence of GBC exhibits significant gender predominance with females two‐threefold higher than males, suggesting oestrogen/oestrogen receptors (ERs) signalling might be a critical driver of tumorigenesis in gallbladder. This study aims to evaluate the antitumour activity of tamoxifen (TAM), a major agent of hormonal therapy for breast cancer, in preclinical GBC model. Quantitative real‐time PCR was used to investigate mRNA levels. Protein expression was measured by immunohistochemistry and Western blot. Glycolytic levels were measured by glucose consumption and lactic acid measurement. The antitumour activity of TAM alone or with cisplatin was examined with CCK8 assay, colony formation, flow cytometry and in vivo models. The results revealed that ERɑ expression was higher in GBC tissues and predicted poor clinical outcomes. TAM was showed effective against a variety of GBC cell lines. Mechanical investigations revealed that TAM enabled potent reactive oxygen species (ROS) production by reduced nuclear factor Nrf2 expression and its target genes, leading to the activation of AMPK, which subsequently induced impaired glycolysis and survival advantages. Notably, TAM was demonstrated to sensitize GBC cells to cisplatin (CDDP) both in vitro and in vivo. In agreement with these findings, elimination of oestrogens by ovariectomy in nude mice prevented CDDP resistance. In summary, these results provide basis for TAM treatment for GBC and shed novel light on the potential application of endocrine therapy for patients with GBC.
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- 2019
9. SPARC promotes pancreatic cancer cell proliferation and migration through autocrine secretion into the extracellular milieu
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Kehua Pan, Xiufen Jia, and Xince Huang
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0301 basic medicine ,Cancer Research ,Stromal cell ,proliferation ,Cell ,pancreatic cancer ,pan-cancer ,Biology ,migration ,03 medical and health sciences ,0302 clinical medicine ,Pancreatic cancer ,medicine ,extracellular milieu ,Autocrine signalling ,Oncogene ,Cell growth ,Cancer ,SPARC ,Articles ,Cell cycle ,medicine.disease ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Cancer research - Abstract
SPARC is a secreted glycoprotein that plays a complex and multifaceted role in tumour formation and progression. However, whether SPARC is an oncogene or a tumour suppressor is still unclear. Moreover, SPARC demonstrates potential in clinical pancreatic adenocarcinoma (PAAD) treatment, although it has been identified as an oncogene in some studies and a tumor suppressor in others. In the present study, a pan-cancer analysis of SPARC was carried out using The Cancer genome Atlas data, which demonstrated that SPARC was an oncogene in most cancer types and a cancer suppressor in others. In addition, SPARC expression was significantly upregulated in PAAD and associated with poor prognosis. SPARC also promoted the proliferation and migration of PANC-1 and SW1990 cell lines in vitro. SPARC was detected in the culture supernatant of PAAD cells and pancreatic acinar AR42J cells. SPARC regulated PAAD cell proliferation only when secreted into the extracellular milieu, thus explaining why the prognosis of patients with PAAD is correlated with the SPARC expression of both tumour cells and stromal cells. Collectively, the present findings demonstrated that the function of SPARC was associated with tumour type and that SPARC may represent an important oncogene in PAAD that merits further study.
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- 2021
10. Deoxycholic acid modulates the progression of gallbladder cancer through N
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Ruirong, Lin, Ming, Zhan, Linhua, Yang, Hui, Wang, Hui, Shen, Shuai, Huang, Xince, Huang, Sunwang, Xu, Zijie, Zhang, Weijian, Li, Qiang, Liu, Yongsheng, Shi, Wei, Chen, Jianxiu, Yu, and Jian, Wang
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Male ,Mice, Inbred BALB C ,Adenosine ,Mice, Nude ,Xenograft Model Antitumor Assays ,Article ,Non-coding RNAs ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,HEK293 Cells ,Cell Line, Tumor ,Disease Progression ,Animals ,Humans ,Biliary tract cancer ,Gallbladder Neoplasms ,RNA Interference ,Cell Proliferation ,Deoxycholic Acid ,Cell signalling - Abstract
Bile acids (BAs), well-defined signaling molecules with diverse metabolic functions, play important roles in cellular processes associated with many cancers. As one of the most common BAs, deoxycholic acid (DCA) is originally synthesized in the liver, stored in the gallbladder, and processed in the gut. DCA plays crucial roles in various tumors; however, functions and molecular mechanisms of DCA in gallbladder cancer (GBC) still remain poorly characterized. Here, we analyzed human GBC samples and found that DCA was significantly downregulated in GBC, and reduced levels of DCA was associated with poor clinical outcome in patients with GBC. DCA treatment impeded tumor progression by halting cell proliferation. DCA decreased miR-92b-3p expression in an m6A-dependent posttranscriptional modification manner by facilitating dissociation of METTL3 from METTL3–METTL14–WTAP complex, which increased the protein level of the phosphatase and tensin homolog, a newly identified target of miR-92b-3p, and subsequently inactivated the PI3K/AKT signaling pathway. Our findings revealed that DCA might function as a tumor suppressive factor in GBC at least by interfering with miR-92b-3p maturation, and suggested that DCA treatment could provide a new therapeutic strategy for GBC.
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- 2020
11. PLZF inhibits proliferation and metastasis of gallbladder cancer by regulating IFIT2
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Hui Shen, Xince Huang, Sunwang Xu, Yonglong Zhang, Jian Wang, Ming Zhan, Mohan Man, Yanhua Yao, Shuai Huang, and Min He
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Male ,0301 basic medicine ,Cancer Research ,Epithelial-Mesenchymal Transition ,Immunology ,Down-Regulation ,Mice, Nude ,Article ,Metastasis ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Cell Movement ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Neoplasm Invasiveness ,Promyelocytic Leukemia Zinc Finger Protein ,RNA, Messenger ,STAT1 ,Epithelial–mesenchymal transition ,Neoplasm Metastasis ,lcsh:QH573-671 ,Aged ,Cell Proliferation ,Regulation of gene expression ,biology ,Cell growth ,lcsh:Cytology ,Proteins ,RNA-Binding Proteins ,Cell Biology ,Middle Aged ,Cell cycle ,Prognosis ,medicine.disease ,Gene Expression Regulation, Neoplastic ,Leukemia ,STAT1 Transcription Factor ,Treatment Outcome ,030104 developmental biology ,Tumor progression ,Multivariate Analysis ,biology.protein ,Cancer research ,Female ,Gallbladder Neoplasms ,Apoptosis Regulatory Proteins - Abstract
Gallbladder cancer (GBC) is a malignant cancer with very poor prognosis. Although promyelocytic leukemia zinc-finger protein (PLZF) was reported to be deregulated in numerous cancers and also relevant to clinical prognosis, its role in GBC progression has been little known. In this study, we found PLZF expression was decreased in GBC, correlating to advanced TNM stage, distant metastasis, and shorter overall survival. Moreover, ectopic PLZF expression in GBC cells (NOZ and GBC-SD) significantly reduced the cell proliferation, migration, and invasion. Consistently, overexpression of PLZF in xenograft mice model could suppress tumor growth and liver metastasis. Mechanical investigations verified PLZF could regulate the expression of cell cycle arrest-associated gene p21 and epithelial–mesenchymal transition (EMT)-related genes (E-cadherin and N-cadherin) in GBC cell lines. Importantly, PLZF remarkably increased the mRNA transcription of interferon-induced protein with tetratricopeptide repeat 2 (IFIT2) by increasing STAT1 protein level, a known factor involved in tumor progression. Furthermore, ablation of IFIT2 in PLZF overexpression cells abrogated the tumor-suppressive function of PLZF, at least partially, leading to impaired tumor growth and EMT program. These studies indicated PLZF inhibited the proliferation and metastasis via regulation of IFIT2. In conclusion, our study demonstrated PLZF could be a promising tumor biomarker for GBC, and also be a potential therapeutic target.
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- 2018
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12. Brusatol inhibits growth and induces apoptosis in pancreatic cancer cells via JNK/p38 MAPK/NF-κb/Stat3/Bcl-2 signaling pathway
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Dinglai Yu, Bicheng Chen, Mengtao Zhou, Bin Lou, Chaohao Huang, Jie Zhang, Yukai Xiang, Wen Ye, and Xince Huang
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STAT3 Transcription Factor ,0301 basic medicine ,MAP Kinase Signaling System ,p38 mitogen-activated protein kinases ,Biophysics ,Antineoplastic Agents ,Apoptosis ,p38 Mitogen-Activated Protein Kinases ,Biochemistry ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Pancreatic cancer ,Tumor Cells, Cultured ,medicine ,Humans ,STAT3 ,Molecular Biology ,Cell Proliferation ,Quassins ,biology ,JNK Mitogen-Activated Protein Kinases ,NF-kappa B ,NF-κB ,Cell Biology ,biology.organism_classification ,medicine.disease ,Cell biology ,Pancreatic Neoplasms ,030104 developmental biology ,Proto-Oncogene Proteins c-bcl-2 ,chemistry ,Brucea ,030220 oncology & carcinogenesis ,Cancer research ,biology.protein ,Signal transduction - Abstract
Brusatol, isolated from brucea, has been proved to exhibit anticancer influence on various kind of human malignancies. However, the role that brusatol plays in pancreatic cancer is seldom known by the public. Through researches brusatol was proved to inhibit growth and induce apoptosis in both PATU-8988 and PANC-1 cells by decreasing the expression level of Bcl-2 and increasing the expression levels of Bax, Cleaved Caspase-3. Then we found the activation of the JNK, p38 MAPK and inactivation of the NF-κb, Stat3 are related with the potential pro-apoptotic signaling pathways. However, SP600125 could not only abrogated the JNK activation caused by brusatol, but also reverse the p38 activation and the decrease of Bcl-2 as SB203580 did. Besides, SP600125 and SB203580 also reversed the inactivation of NF-κb and Stat3. Furthermore, BAY 11-7082 and S3I-201 indeed had the similar effect as brusatol had on the expression of Phospho-Stat3 and Bcl-2. To sum up, we came to a conclusion that in pancreatic cancer, brusatol do inhibit growth and induce apoptosis. And we inferred that brusatol illustrates anticancer attribution via JNK/p38 MAPK/NF-κb/Stat3/Bcl-2 signaling pathway.
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- 2017
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13. Circular RNA circERBB2 promotes gallbladder cancer progression by regulating PA2G4-dependent rDNA transcription
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Wei Cheng, Sunwang Xu, Xince Huang, Jian Wang, Ming Zhan, Dong Yang, Zilong Qiu, Jianxiu Yu, Shuai Huang, Ruirong Lin, Ming He, and Hui Shen
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0301 basic medicine ,Cancer Research ,Nucleolus ,Receptor, ErbB-2 ,rDNA ,Biology ,lcsh:RC254-282 ,Ribosome ,DNA, Ribosomal ,Models, Biological ,03 medical and health sciences ,0302 clinical medicine ,Western blot ,Transcription (biology) ,Circular RNA ,Cell Line, Tumor ,medicine ,Biomarkers, Tumor ,Humans ,Adaptor Proteins, Signal Transducing ,medicine.diagnostic_test ,Gene Expression Profiling ,Research ,RNA ,RNA-Binding Proteins ,RNA, Circular ,circERBB2 ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Prognosis ,Gallbladder cancer ,Oncogene ErbB2 ,Cell biology ,Gene Expression Regulation, Neoplastic ,Alternative Splicing ,030104 developmental biology ,Oncology ,ROC Curve ,030220 oncology & carcinogenesis ,PA2G4 ,Disease Progression ,Molecular Medicine ,Gallbladder Neoplasms ,Fluorescence in situ hybridization - Abstract
Background CircRNAs are found to affect initiation and progression of several cancer types. However, whether circRNAs are implicated in gallbladder cancer (GBC) progression remains obscure. Methods We perform RNA sequencing in 10 pairs of GBC and para-cancer tissues. CCK8 and clone formation assays are used to evaluate proliferation ability of GBC cells. qPCR and Western blot are used to determine expression of RNAs and proteins, respectively. CircRNA-protein interaction is confirmed by RNA pulldown, RNA immunoprecipitation, and fluorescence in situ hybridization. Results We find that circRNA expression pattern is tremendously changed during GBC development. Among dozens of significantly changed circRNAs, a circRNA generated from the oncogene ERBB2, named as circERBB2, is one of the most significant changes. CircERBB2 promotes GBC proliferation, in vitro and in vivo. Other than being a miRNA sponge, circERBB2 accumulates in the nucleoli and regulates ribosomal DNA transcription, which is one of the rate-limiting steps of ribosome synthesis and cellular proliferation. CircERBB2 regulates nucleolar localization of PA2G4, thereby forming a circERBB2-PA2G4-TIFIA regulatory axis to modulate ribosomal DNA transcription and GBC proliferation. Increased expression of circERBB2 is associated with worse prognosis of GBC patients. Conclusions Our findings demonstrate that circERBB2 serves as an important regulator of cancer cell proliferation and shows the potential to be a new therapeutic target of GBC.
- Published
- 2019
14. PLEK2 promotes gallbladder cancer invasion and metastasis through EGFR/CCL2 pathway
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Man Mohan, Xince Huang, Wei Chen, Yanhua Yao, Ming Zhan, Sunwang Xu, Jian Wang, Hui Shen, Min He, Chu Xu, and Ruirong Lin
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Male ,0301 basic medicine ,Cancer Research ,Chemokine ,Microarray ,Metastasis ,Mice ,0302 clinical medicine ,Cell Movement ,Neoplasm Metastasis ,Chemokine CCL2 ,Aged, 80 and over ,medicine.diagnostic_test ,biology ,Middle Aged ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Prognosis ,Immunohistochemistry ,ErbB Receptors ,Oncology ,030220 oncology & carcinogenesis ,Gallbladder Neoplasms ,CCL2 ,Protein Binding ,Signal Transduction ,EGFR ,lcsh:RC254-282 ,03 medical and health sciences ,Western blot ,Downregulation and upregulation ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Neoplasm Invasiveness ,Gallbladder cancer ,PLEK2 ,Aged ,Cell Proliferation ,Neoplasm Staging ,Research ,Membrane Proteins ,Gallbladder Cancer ,medicine.disease ,030104 developmental biology ,Apoptosis ,biology.protein ,Cancer research ,Biomarkers - Abstract
Background Gallbladder cancer (GBC) is an extremely malignant tumor with a high mortality rate. Little is known about its invasion and metastasis mechanism so far. Methods To identify the driver genes in GBC metastasis, we performed a mRNA microarray of metastatic GBC and paired non-tumor samples, and found PLEK2 was markedly upregulated in GBC tissues. Next, the expression of PLEK2 in GBC were examined in a larger cohort of patients by qRT-PCR, western blot and IHC staining. The clinicopathologic correlation of PLEK2 was determined by statistical analyses. The biological involvement of PLEK2 in GBC metastasis and the underlying mechanisms were investigated. Results In this study, we found that PLEK2 had higher expression in GBC tumor tissues compared to non-cancerous adjacent tissues and cholecystolithiasis tissues. The clinicopathologic analyses showed PLEK2 expression was positively correlated with tumor TNM stage, distant metastasis and PLEK2 was an independent predictor of overall survival (OS) in GBC patients. The cellular function assays showed PLEK2 promoted GBC cells migration, invasion and liver metastasis in mouse model via the regulation of epithelial-mesenchymal transition (EMT) process. Our mass spectrum and co-immunoprecipitation (co-IP) assays demonstrated that PLEK2 could interact with the kinase domain of EGFR and suppress EGFR ubiquitination mediated by c-CBL, leading to constitutive activation of EGFR signaling. Furthermore, RNA-sequencing and qRT-PCR results demonstrated chemokine (C-C motif) ligand 2 (CCL2), a target gene downstream of PLEK2/EGFR signaling, mediated the motility-promoting function of PLEK2. Conclusions On the basis of these collective data, we propose that PLEK2 promotes the invasion and metastasis of GBC by EGFR/CCL2 pathway and PLEK2 can serve as a potential therapeutic target for GBC treatment. Electronic supplementary material The online version of this article (10.1186/s13046-019-1250-8) contains supplementary material, which is available to authorized users.
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- 2019
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15. Additional file 6: of PLEK2 promotes gallbladder cancer invasion and metastasis through EGFR/CCL2 pathway
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Shen, Hui, He, Min, Ruirong Lin, Zhan, Ming, Sunwang Xu, Xince Huang, Xu, Chu, Chen, Wei, Yanhua Yao, Mohan, Man, and Wang, Jian
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Figure S4B. EGFR mRNA levels of NOZ and GBC-SD cells with stable PLEK2 knockdown and overexpression were detected by qRT-PCR. (PDF 118 kb)
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- 2019
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16. Additional file 9: of PLEK2 promotes gallbladder cancer invasion and metastasis through EGFR/CCL2 pathway
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Shen, Hui, He, Min, Ruirong Lin, Zhan, Ming, Sunwang Xu, Xince Huang, Xu, Chu, Chen, Wei, Yanhua Yao, Mohan, Man, and Wang, Jian
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Figure S5. Representative images of H&E staining of mouse model. Figure S5A and S5B were the representative images of H&E staining of metastatic focuses in livers, Figure S5C was a representative image of the H&E staining of subcutaneous xenografts. (PDF 1697 kb)
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- 2019
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17. Additional file 2: of PLEK2 promotes gallbladder cancer invasion and metastasis through EGFR/CCL2 pathway
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Shen, Hui, He, Min, Ruirong Lin, Zhan, Ming, Sunwang Xu, Xince Huang, Xu, Chu, Chen, Wei, Yanhua Yao, Mohan, Man, and Wang, Jian
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Figure S2A. Cells construction of PLEK2 down-regulation NOZ and GBC-SD cells (NOZ-shPLEK2, GBC-SD-shPLEK2, respectively), also PLEK2 overexpression NOZ and GBC-SD cells (NOZ-PLEK2, GBC-SD-PLEK2, respectively). (PDF 95 kb)
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- 2019
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18. Additional file 7: of PLEK2 promotes gallbladder cancer invasion and metastasis through EGFR/CCL2 pathway
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Shen, Hui, He, Min, Ruirong Lin, Zhan, Ming, Sunwang Xu, Xince Huang, Xu, Chu, Chen, Wei, Yanhua Yao, Mohan, Man, and Wang, Jian
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Figure S4C. GBC cells were treated with 100 μM Chloroquine for 8 h, followed by 50 ng/ml EGF stimulation for 5 m. Alterations of EGFR expression in PLEK2 knockdown cells were detected by western blot. (PDF 139 kb)
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- 2019
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19. Additional file 8: of PLEK2 promotes gallbladder cancer invasion and metastasis through EGFR/CCL2 pathway
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Shen, Hui, He, Min, Ruirong Lin, Zhan, Ming, Sunwang Xu, Xince Huang, Xu, Chu, Chen, Wei, Yanhua Yao, Mohan, Man, and Wang, Jian
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fungi - Abstract
Figure S4D. Protein levels of EGFR in PLEK2 overexpression cells with increasing ectopic c-CBL expression were detected by western blot. (PDF 93 kb)
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- 2019
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20. Additional file 1: of PLEK2 promotes gallbladder cancer invasion and metastasis through EGFR/CCL2 pathway
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Shen, Hui, He, Min, Ruirong Lin, Zhan, Ming, Sunwang Xu, Xince Huang, Xu, Chu, Chen, Wei, Yanhua Yao, Mohan, Man, and Wang, Jian
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Figure S1A. Analysis the gene expression differences and its distribution in human cancer cells by bioinformatics data ( http://www.broadinstitute.o.rg ). (PDF 145 kb)
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- 2019
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21. Additional file 4 of PLEK2 promotes gallbladder cancer invasion and metastasis through EGFR/CCL2 pathway
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Shen, Hui, He, Min, Ruirong Lin, Zhan, Ming, Sunwang Xu, Xince Huang, Xu, Chu, Chen, Wei, Yanhua Yao, Mohan, Man, and Wang, Jian
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fungi - Abstract
Figure S2C. EMT markers of NOZ and GBC-SD cells with stable PLEK2 knockdown and overexpression were detected by qRT-PCR. (PDF 186 kb)
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- 2019
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22. Isoorientin induces apoptosis, decreases invasiveness, and downregulates VEGF secretion by activating AMPK signaling in pancreatic cancer cells
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Tingting Ye, Mengtao Zhou, Chaohao Huang, Shengjie Dai, Xince Huang, Bicheng Chen, Dinglai Yu, and Jiadong Su
- Subjects
AMPK ,isoorientin ,0301 basic medicine ,Isoorientin ,invasiveness ,pancreatic cancer ,Biology ,OncoTargets and Therapy ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Pharmacology (medical) ,Protein kinase A ,Original Research ,apoptosis ,Transfection ,VEGF ,Cell biology ,Vascular endothelial growth factor ,030104 developmental biology ,Oncology ,chemistry ,Apoptosis ,030220 oncology & carcinogenesis ,Signal transduction ,Luteolin - Abstract
Tingting Ye,1 Jiadong Su,1 Chaohao Huang,1 Dinglai Yu,1 Shengjie Dai,1 Xince Huang,1 Bicheng Chen,1,2 Mengtao Zhou1 1Department of Surgery, The First Affiliated Hospital, Wenzhou Medical University, 2Zhejiang Provincial Top Key Discipline in Surgery, Wenzhou Key Laboratory of Surgery, Wenzhou, Zhejiang Province, People’s Republic of China Abstract: Isoorientin (or homoorientin) is a flavone, which is a chemical flavonoid-like compound, and a 6-C-glucoside of luteolin. Isoorientin has been demonstrated to have anti-cancer activities against various tumors, but its effects on pancreatic cancer (PC) have not been studied in detail. In this study, we aim to investigate whether isoorientin has potential anti-PC effects and its underlying mechanism. In PC, isoorientin strongly inhibited the survival of the cells, induced cell apoptosis, and decreased its malignancy by reversing the expression of epithelial–mesenchymal transition and matrix metalloproteinase and decreased vascular endothelial growth factor expression. Meanwhile, we investigated the activity of the AMP-activated protein kinase (AMPK) signaling pathway after isoorientin treatment, which was forcefully activated by isoorientin, as expected. In addition, in the PC cells that were transfected with lentivirus to interfere with the expression of the gene PRKAA1, there were no differences in the apoptosis rate and the expression of malignancy biomarkers in the tumors of the isoorientin-treated and untreated groups. Thus, we demonstrated that isoorientin has potential antitumor effects via the AMPK signaling pathway, and isoorientin merits further investigation. Keywords: pancreatic cancer, AMPK, isoorientin, apoptosis, invasiveness, VEGF
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- 2016
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23. Tamoxifen Sensitizes Gallbladder Cancer to Cisplatin Resistance by Impaired Glucose Metabolism via Activation of AMPK Signaling
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Sunwang Xu, Jian Wang, Hui Wang, Ruirong Lin, Wei Chen, Shuai Huang, Hui Shen, Xince Huang, and Ming Zhan
- Subjects
Cisplatin ,medicine.drug_class ,business.industry ,Estrogen receptor ,AMPK ,medicine.disease_cause ,medicine.disease ,Estrogen ,medicine ,Cancer research ,Hormonal therapy ,Gallbladder cancer ,Carcinogenesis ,business ,Tamoxifen ,medicine.drug - Abstract
Purpose: Gallbladder cancer (GBC) is the leading malignancy of biliary system showing refractory chemoresistance to current first-line drugs. Growing epidemiological evidences have established that the incidence of GBC exhibits significant gender predominance with females 2-3 fold higher than males, suggesting estrogen/estrogen receptors (ERs) signaling might be a critical driver of tumorigenesis in gallbladder. This study aims to evaluate the antitumor activity of tamoxifen (TAM), a major agent of hormonal therapy for breast cancer, in preclinical GBC model. Experimental Design: The antitumor activity of TAM alone or with cisplatin was examined using cell viability, apoptosis and in vivo models. Results: Increased ERɑ expression was found in GBC tissues and predicted poor clinical outcomes. TAM was showed effective against a variety of GBC cell lines. Mechanical investigations revealed that TAM enabled potent reactive oxygen species (ROS) production by reduced nuclear factor (erythroid-derived 2)-like 2(Nrf2) expression and its target genes, leading to the activation of Adenosine Monophosphate Activated Protein Kinase (AMPK), which subsequently induced impaired glycolysis and survival advantages. Moreover, the inhibitory effect of TAM for GBC cells was remarkably attenuated by N-acetyl-L-cysteine (NAC) and AMPK inhibitor, suggesting ROS/AMPK axis was required for TAM tumor-suppressive function. Notably, TAM was demonstrated to sensitize GBC cells to cisplatin (CDDP) both in vitro and in vivo. In agreement with these findings, elimination of estrogens by ovariectomy in nude mice prevented CDDP resistance. Conclusions: These results provide basis for TAM-mediated chemosensitivity for GBC and shed novel light on the potential application of endocrine therapy for patients with GBC. Funding Statement: This work was supported by National Science Foundation of China (81472240,81272748 and 81072011),Science and Technology Commission of Shanghai Municipality (16411952700, 10411955400, and 09411960800), Program for Outstanding Academic Leader of Shanghai (2016, JW) Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: The collection and analysis of patient samples were approved by the Ethical Committee of Renji Hospital, Shanghai Jiao Tong University School of Medicine, and written informed consent was obtained from all patients. All methods and experiments were carried out in accordance with the approved guidelines and regulations. Animal maintenance and experimental procedures were strictly performed following the guidelines of the Animal Care and Use Committee of Shanghai Jiao Tong University and approved by IACUC committee of Shanghai Jiao Tong University
- Published
- 2018
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24. Luteolin inhibits pancreatitis‑induced acinar‑ductal metaplasia, proliferation and epithelial‑mesenchymal transition of acinar cells
- Author
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Tingting Ye, Gang Fan, Pravin Avinash Bhugul, Mengtao Zhou, Xince Huang, Shengjie Dai, Bicheng Chen, and Shihao Huang
- Subjects
Male ,STAT3 Transcription Factor ,0301 basic medicine ,Cancer Research ,Epithelial-Mesenchymal Transition ,Down-Regulation ,Vimentin ,Acinar Cells ,Biochemistry ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,acinar-ductal metaplasia ,Pancreatic cancer ,Metaplasia ,Genetics ,medicine ,Animals ,Epithelial–mesenchymal transition ,luteolin ,Pancreas ,Molecular Biology ,Cells, Cultured ,Cell Proliferation ,pancreatic carcinogenesis ,Keratin-19 ,biology ,Chemistry ,SOX9 Transcription Factor ,Articles ,medicine.disease ,Immunohistochemistry ,ErbB Receptors ,Mice, Inbred C57BL ,030104 developmental biology ,Pancreatitis ,Oncology ,Apoptosis ,Acute Disease ,biology.protein ,Cancer research ,Molecular Medicine ,Ectopic expression ,medicine.symptom ,Luteolin ,SOX9 ,Signal Transduction - Abstract
Luteolin, a flavone, has been demonstrated to have anti‑cancer properties. In the current study, the effects of luteolin on certain carcinogenesis‑associated changes induced by pancreatitis, which are significant risk factors for pancreatic cancer, were investigated. Male six‑week‑old C57BL6 mice used in the current study were divided into three groups; the control group, acute pancreatitis group and luteolin group. Intra‑peritoneal injection of cearulein was performed in the acute pancreatitis group and luteolin group to induce acute pancreatitis whereas the luteolin group received intra‑peritoneal injection of luteolin. The control group received intra‑peritoneal injection of normal saline. Then, the expression of SOX9, phosphorylated (p‑) STAT3, p‑EGFR, cytokeratin‑19, Ki67 and N‑cadherin were determined by immunohistochemistry. Morphological changes of acinar cells were determined by hematoxylin and eosin staining. The mRNA expression of the epithelial‑mesenchymal transition markers CDH1, CDH2, Slug, Zeb1, EpCAM, ZO1, Vimentin, Snail and Twist was determined by reverse transcription‑quantitative polymerase chain reaction. It was identified that luteolin inhibits the formation of tubular complexes and ectopic expression of cytokeratin‑19 and luteolin also decreased proteins of SOX9, p‑STAT3 and p‑EGFR. In addition, luteolin inhibits proliferation and epithelial‑mesenchymal transition of acinar cells induced by acute pancreatitis. As tubular complex formation and ectopic expression of cytokeratin‑19 were two prominent characters of acinar‑ductal metaplasia, it was concluded that luteolin inhibits acinar‑ductal metaplasia induced by pancreatitis and also inhibits pancreatitis‑induced proliferation and epithelial‑mesenchymal transition of acinar cells. Acinar‑ductal metaplasia and proliferation have close associations with pancreatic carcinogenesis. It is suggested that luteolin has potential anti‑pancreatic carcinogenesis effects and merits further investigation.
- Published
- 2017
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25. Reduced Pancreatic Exocrine Function and Organellar Disarray in a Canine Model of Acute Pancreatitis
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Qiang Li, Lewei Liu, Hongwei Sun, Mengtao Zhou, Xince Huang, Pravin Avinash Bhugul, Qiyu Zhang, Haizhen Ni, Liangliang Pan, Michael Hehir, Bicheng Chen, Yuepeng Jin, and Yongyu Bai
- Subjects
0301 basic medicine ,Pathology ,Hydrolases ,Physiology ,lcsh:Medicine ,Endoplasmic Reticulum ,Biochemistry ,Edema ,Medicine and Health Sciences ,Lipases ,lcsh:Science ,Energy-Producing Organelles ,Mammals ,Multidisciplinary ,Secretory Pathway ,Pancreas, Exocrine ,Enzymes ,Mitochondria ,Chemistry ,medicine.anatomical_structure ,Cell Processes ,Vertebrates ,Physical Sciences ,Acute Disease ,Amylases ,Acute pancreatitis ,medicine.symptom ,Anatomy ,Cellular Structures and Organelles ,Pancreas ,Research Article ,medicine.medical_specialty ,Endocrine System ,Biology ,Bioenergetics ,03 medical and health sciences ,Exocrine Glands ,Dogs ,Internal medicine ,medicine ,Acinar cell ,Animals ,Secretion ,Pancreatic duct ,Organelles ,Endoplasmic reticulum ,lcsh:R ,Organisms ,Pancreatic Ducts ,Chemical Compounds ,Biology and Life Sciences ,Proteins ,Extracellular Fluid ,Cell Biology ,Lipase ,medicine.disease ,Bicarbonates ,Disease Models, Animal ,030104 developmental biology ,Endocrinology ,Pancreatitis ,Rough Endoplasmic Reticulum ,Enzymology ,Hyperamylasemia ,lcsh:Q ,Physiological Processes - Abstract
The aim of the present study was to investigate the pancreatic exocrine function in a canine model and to analyze the changes in organelles of pancreatic acinar cells during the early stage of acute pancreatitis (AP). AP was induced by retrograde injection of 5% sodium taurocholate (0.5 ml/kg) into the main pancreatic duct of dogs. The induction of AP resulted in serum hyperamylasemia and a marked reduction of amylase activity in the pancreatic fluid (PF). The pancreatic exocrine function was markedly decreased in subjects with AP compared with the control group. After the induction of AP, histological examination showed acinar cell edema, cytoplasmic vacuolization, fibroblasts infiltration, and inflammatory cell infiltration in the interstitium. Electron micrographs after the induction of AP revealed that most of the rough endoplasmic reticulum (RER) were dilated and that some of the ribosomes were no longer located on the RER. The mitochondria were swollen, with shortened and broken cristae. The present study demonstrated, in a canine model, a reduced volume of PF secretion with decreased enzyme secretion during the early stage of AP. Injury of mitochondria and dilatation and degranulation of RER may be responsible for the reduced exocrine function in AP. Furthermore, the present model and results may be useful for researching novel therapeutic measures in AP.
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- 2016
26. Luteolin decreases invasiveness, deactivates STAT3 signaling, and reverses interleukin-6 induced epithelial-mesenchymal transition and matrix metalloproteinase secretion of pancreatic cancer cells
- Author
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Bicheng Chen, Xince Huang, Shengjie Dai, Juji Dai, Yongyu Bai, Yuwu Xiao, and Mengtao Zhou
- Subjects
MMP2 ,matrix metalloproteinase ,MMP9 ,Matrix metalloproteinase ,epithelial–mesenchymal transition ,MMP7 ,OncoTargets and Therapy ,STAT3 ,chemistry.chemical_compound ,Pancreatic cancer ,medicine ,Pharmacology (medical) ,Epithelial–mesenchymal transition ,luteolin ,Original Research ,biology ,business.industry ,medicine.disease ,Oncology ,chemistry ,Immunology ,Cancer research ,biology.protein ,business ,Luteolin - Abstract
Xince Huang,1 Shengjie Dai,1 Juji Dai,1 Yuwu Xiao,1 Yongyu Bai,1 Bicheng Chen,1,2 Mengtao Zhou1 1Department of Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang Province, People’s Republic of China; 2Zhejiang Provincial Top Key Discipline in Surgery, Wenzhou Key Laboratory of Surgery, Wenzhou, Zhejiang Province, People’s Republic of China Abstract: Luteolin, a flavone, has been shown to exhibit anticancer properties. Here, we investigated whether luteolin affects epithelial–mesenchymal transition (EMT) and invasiveness of pancreatic cancer cell lines and their underlying mechanism. Pancreatic cancer cell lines PANC-1 and SW1990 were used in our study, and their EMT characters, matrix metalloproteinase (MMP) expression level, invasiveness, and signal transducer and activator of transcription 3 (STAT3) activity were determined after luteolin treatment. We also treated pancreatic cancer cells with interleukin-6 (IL-6) to see whether IL-6-induced activation of STAT3, EMT, and MMP secretion was affected by luteolin. We found that luteolin inhibits EMT and MMP2, MMP7, and MMP9 expression in a dose-dependent manner, similar to STAT3 signaling. Through Transwell assay, we found that invasiveness of pancreatic cancer cells was inhibited by luteolin. EMT characters and MMP secretion increase with STAT3 activity after IL-6 treatment and these effects, caused by IL-6, were inhibited by luteolin. We concluded that luteolin inhibits invasiveness of pancreatic cancer cells, and we speculated that luteolin inhibits EMT and MMP secretion likely through deactivation of STAT3 signaling. Luteolin has potential antitumor effects and merits further investigation. Keywords: epithelial–mesenchymal transition, matrix metalloproteinase, luteolin, STAT3
- Published
- 2015
27. HNRNPA2B1 regulates the epithelial-mesenchymal transition in pancreatic cancer cells through the ERK/snail signalling pathway.
- Author
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Shengjie Dai, Jie Zhang, Shihao Huang, Bin Lou, Binbo Fang, Tingting Ye, Xince Huang, Bicheng Chen, and Mengtao Zhou
- Subjects
NUCLEOPROTEINS ,TUMORS ,METASTASIS ,MESENCHYMAL stem cells ,PANCREATIC cancer - Abstract
Background: Heterogeneous nuclear ribonucleoprotein A2B1 (HNRNPA2B1) is closely related to tumour occurrence and development, oncogene expression, apoptosis inhibition and invasion and metastasis capacities. However, its function in the epithelial-mesenchymal transition (EMT) of pancreatic cancer is not fully understood. Methods: By comparing various wild-type pancreatic cancer cell lines, we determined which have a higher expression level of HNRNPA2B1 accompanied by the higher expression of N-cadherin and vimentin and lower expression of E-cadherin. Therefore, to elucidate the role of HNRNPA2B1 in EMT, we generated models of HNRNPA2B1 knockdown and overexpression in different types of pancreatic cancer cell lines (MIA Paca-2, PANC-1 and Patu-8988) and examined changes in expression of EMT-related factors, including CDH1, CDH2, vimentin and snail. Results: The results show that HNRNPA2B1 promotes EMT development by down-regulating E-cadherin and upregulating N-cadherin and vimentin, and also stimulates the invasion capacity and inhibits viability in human pancreatic cancer cell lines, the similar results in vivo experiments. Moreover, we found that HNRNPA2B1 likely regulates EMT progression in pancreatic carcinoma via the ERK/snail signalling pathway. Conclusions: The results of this work suggest that HNRNPA2B1 inhibition has potential antitumour effects, which warrants in-depth investigation. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
28. Isoorientin induces apoptosis, decreases invasiveness, and downregulates VEG F secretion by activating AMPK signaling in pancreatic cancer cells.
- Author
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Tingting Ye, Jiadong Su, Chaohao Huang, Dinglai Yu, Shengjie Dai, Xince Huang, Bicheng Chen, and Mengtao Zhou
- Subjects
PANCREATIC cancer ,PHYSIOLOGICAL effects of flavonoids ,APOPTOSIS ,VASCULAR endothelial growth factors ,PROTEIN kinases ,CELLULAR signal transduction - Abstract
Isoorientin (or homoorientin) is a flavone, which is a chemical flavonoid-like compound, and a 6-C-glucoside of luteolin. Isoorientin has been demonstrated to have anti-cancer activities against various tumors, but its effects on pancreatic cancer (PC) have not been studied in detail. In this study, we aim to investigate whether isoorientin has potential anti-PC effects and its underlying mechanism. In PC, isoorientin strongly inhibited the survival of the cells, induced cell apoptosis, and decreased its malignancy by reversing the expression of epithelial- mesenchymal transition and matrix metalloproteinase and decreased vascular endothelial growth factor expression. Meanwhile, we investigated the activity of the AMP-activated protein kinase (AMPK) signaling pathway after isoorientin treatment, which was forcefully activated by isoorientin, as expected. In addition, in the PC cells that were transfected with lentivirus to interfere with the expression of the gene PRKAA1, there were no differences in the apoptosis rate and the expression of malignancy biomarkers in the tumors of the isoorientin-treated and untreated groups. Thus, we demonstrated that isoorientin has potential antitumor effects via the AMPK signaling pathway, and isoorientin merits further investigation. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
29. Dexamethasone shifts bone marrow stromal cells from osteoblasts to adipocytes by C/EBPalpha promoter methylation
- Author
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Jiake Xu, Xince Huang, Ning Zhang, Julio Cesar B. Fernandes, Jichang Li, Xiaoling Zhang, and Kerong Dai
- Subjects
Male ,Cancer Research ,medicine.medical_specialty ,endocrine system ,Stromal cell ,Immunology ,Bone Morphogenetic Protein 2 ,Biology ,Bone morphogenetic protein 2 ,Dexamethasone ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,BMSC differentiation ,Mice ,Bone Density ,Osteogenesis ,Adipocyte ,Internal medicine ,medicine ,polycyclic compounds ,Adipocytes ,CCAAT-Enhancer-Binding Protein-alpha ,Animals ,Humans ,Promoter Regions, Genetic ,Wnt Signaling Pathway ,C/EBPalpha ,Adiposity ,DNA methylation ,Adipogenesis ,Osteoblasts ,Wnt signaling pathway ,Wnt/beta-catenin ,Osteoblast ,Mesenchymal Stem Cells ,Cell Biology ,osteoporosis ,Mice, Inbred C57BL ,Endocrinology ,medicine.anatomical_structure ,chemistry ,Gene Knockdown Techniques ,Cancer research ,Original Article ,Bone marrow ,Lithium Chloride ,hormones, hormone substitutes, and hormone antagonists - Abstract
Dexamethasone (Dex)-induced osteoporosis has been described as the most severe side effect in long-term glucocorticoid therapy. The decreased bone mass and the increased marrow fat suggest that Dex possibly shifts the differentiation of bone marrow stromal cells (BMSCs) to favor adipocyte over osteoblast, but the underlying mechanisms are still unknown. In this paper, we established a Dex-induced osteoporotic mouse model, and found that BMSCs from Dex-treated mice are more likely to differentiate into adipocyte than those from control mice, even under the induction of bone morphogenetic protein-2 (BMP2). We also discovered both in vitro and in vivo that the expression level of adipocyte regulator CCAAT/enhancer-binding protein alpha (C/EBPalpha) is significantly upregulated in Dex-induced osteoporotic BMSCs during osteoblastogenesis by a mechanism that involves inhibited DNA hypermethylation of its promoter. Knockdown of C/EBPalpha in Dex-induced osteoporotic cells rescues their differentiation potential, suggesting that Dex shifts BMSC differentiation by inhibiting C/EBPalpha promoter methylation and upregulating its expression level. We further found that the Wnt/beta-catenin pathway is involved in Dex-induced osteoporosis and C/EBPalpha promoter methylation, and its activation by LiCl rescues the effect of Dex on C/EBPalpha promoter methylation and osteoblast/adipocyte balance. This study revealed the C/EBPalpha promoter methylation mechanism and evaluated the function of Wnt/beta-catenin pathway in Dex-induced osteoporosis, providing a useful therapeutic target for this type of osteoporosis.
- Published
- 2013
30. Luteolin decreases invasiveness, deactivates STAT3 signaling, and reverses interleukin-6 induced epithelial--mesenchymal transition and matrix metalloproteinase secretion of pancreatic cancer cells.
- Author
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Xince Huang, Shengjie Dai, Juji Dai, Yuwu Xiao, Yongyu Bai, Bicheng Chen, and Mengtao Zhou
- Subjects
- *
PANCREATIC cancer , *LUTEOLIN , *CANCER cell enzymes , *CELLULAR pathology , *CANCER cells , *CARCINOGENS , *CANCER treatment , *MEDICAL care - Abstract
Luteolin, a flavone, has been shown to exhibit anticancer properties. Here, we investigated whether luteolin affects epithelial-mesenchymal transition (EMT) and invasiveness of pancreatic cancer cell lines and their underlying mechanism. Pancreatic cancer cell lines PANC-1 and SW1990 were used in our study, and their EMT characters, matrix metalloproteinase (MMP) expression level, invasiveness, and signal transducer and activator of transcription 3 (STAT3) activity were determined after luteolin treatment. We also treated pancreatic cancer cells with interleukin-6 (IL-6) to see whether IL-6-induced activation of STAT3, EMT, and MMP secretion was affected by luteolin. We found that luteolin inhibits EMT and MMP2, MMP7, and MMP9 expression in a dose-dependent manner, similar to STAT3 signaling. Through Transwell assay, we found that invasiveness of pancreatic cancer cells was inhibited by luteolin. EMT characters and MMP secretion increase with STAT3 activity after IL-6 treatment and these effects, caused by IL-6, were inhibited by luteolin. We concluded that luteolin inhibits invasiveness of pancreatic cancer cells, and we speculated that luteolin inhibits EMT and MMP secretion likely through deactivation of STAT3 signaling. Luteolin has potential antitumor effects and merits further investigation. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
31. HNRNPA2B1 regulates the epithelial–mesenchymal transition in pancreatic cancer cells through the ERK/snail signalling pathway
- Author
-
Bicheng Chen, Shihao Huang, Binbo Fang, Mengtao Zhou, Bin Lou, Shengjie Dai, Jie Zhang, Tingting Ye, and Xince Huang
- Subjects
0301 basic medicine ,Oncology ,MAPK/ERK pathway ,medicine.medical_specialty ,Cancer Research ,Heterogeneous nuclear ribonucleoprotein ,HNRNPA2B1 ,Vimentin ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Pancreatic cancer ,medicine ,Genetics ,Epithelial–mesenchymal transition ,Oncogene ,biology ,medicine.disease ,Hedgehog signaling pathway ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cancer research ,biology.protein ,ERK/snail ,Primary Research - Abstract
Background Heterogeneous nuclear ribonucleoprotein A2B1 (HNRNPA2B1) is closely related to tumour occurrence and development, oncogene expression, apoptosis inhibition and invasion and metastasis capacities. However, its function in the epithelial–mesenchymal transition (EMT) of pancreatic cancer is not fully understood. Methods By comparing various wild-type pancreatic cancer cell lines, we determined which have a higher expression level of HNRNPA2B1 accompanied by the higher expression of N-cadherin and vimentin and lower expression of E-cadherin. Therefore, to elucidate the role of HNRNPA2B1 in EMT, we generated models of HNRNPA2B1 knockdown and overexpression in different types of pancreatic cancer cell lines (MIA Paca-2, PANC-1 and Patu-8988) and examined changes in expression of EMT-related factors, including CDH1, CDH2, vimentin and snail. Results The results show that HNRNPA2B1 promotes EMT development by down-regulating E-cadherin and up-regulating N-cadherin and vimentin, and also stimulates the invasion capacity and inhibits viability in human pancreatic cancer cell lines, the similar results in vivo experiments. Moreover, we found that HNRNPA2B1 likely regulates EMT progression in pancreatic carcinoma via the ERK/snail signalling pathway. Conclusions The results of this work suggest that HNRNPA2B1 inhibition has potential antitumour effects, which warrants in-depth investigation.
- Full Text
- View/download PDF
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