title: Loss of MicroRNA-101 Promotes Epithelial to Mesenchymal Transition in Hepatocytes.
abstract: Epithelial-to-mesenchymal transition (EMT) has been implicated in embryonic development and various pathological events. However, the involvement of microRNA in the process of EMT remains to be fully defined in hepatocyte. ZEB1 is a well-known transcriptional repressor of E-cadherin and plays a major role in triggering EMT during organ fibrosis and cancer cell metastasis. Computational microRNA target predictions detect a conserved sequence matching to miR-101 in the 3'UTR of ZEB1 mRNA. Our results confirm that miR-101 suppresses ZEB1 expression by targeting the predicted site of ZEB1 3'UTR. Subsequent investigations show that miR-101 is significantly downregulated in the cultured hepatocytes undergoing EMT and in the hepatocytes isolated from fibrotic liver. Along with the loss of miR-101, the ZEB1 expression increases simultaneously in hepatocytes. In addition, miR-101 levels in HCC cell lines are negatively associated with the ZEB1 productions and the metastatic potentials of tumor cells. Mechanistically, we demonstrate that miR-101 significantly inhibits the TGF-β1-induced EMT in hepatocytes, whereas inhibition of miR-101 promotes the EMT process as indicated by the changes of morphology, cell migration, and the expression profiles of EMT markers. In the fibrotic liver, ectopic expression of miR-101 can significantly downregulate ZEB1 in the hepatocyte and thereby reduces the mesenchymal marker expression. Moreover, miR-101 significantly inhibits the proliferation and migration of HCC cell. Our results demonstrate that miR-101 regulates HCC cell phenotype by upregulating the epithelial marker genes and suppressing the mesenchymal ones.
authors: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing, PR China.
authors: Shuhua
authors: S
authors: Zhao
authors: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing, PR China.
authors: Yuanyuan
authors: Y
authors: Zhang
authors: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing, PR China.
authors: Xiuxiu
authors: X
authors: Zheng
authors: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing, PR China.
authors: Xiaolong
authors: X
authors: Tu
authors: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing, PR China.
authors: Huanan
authors: H
authors: Li
authors: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing, PR China.|State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing, PR China.
authors: Jiangning
authors: J
authors: Chen
authors: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing, PR China.|State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing, PR China.
authors: Yuhui
authors: Y
authors: Zang
authors: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing, PR China.|Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, Nanjing, PR China.
authors: Junfeng
authors: J
authors: Zhang
mesh_terms: D020413:3' Untranslated Regions; D015820:Cadherins / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D009362:Neoplasm Metastasis; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: D020413:3' Untranslated Regions; D015820:Cadherins; D018398:Homeodomain Proteins; C534072:MIRN101 microRNA, human; D035683:MicroRNAs; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1