title: miR-139-5p inhibits epithelial-mesenchymal transition, migration and invasion of hepatocellular carcinoma cells by targeting ZEB1 and ZEB2.
abstract: Hepatocellular carcinoma (HCC) is the third most common cause of cancer deaths worldwide. miRNAs have been suggested to have important roles in HCC development. The purpose of this study was to determine the role of miR-139-5p in regulation of epithelial-mesenchymal transition (EMT) and metastasis of HCC cells. Expression levels of miR-139-5p in 49 HCC specimens with adjacent tissues and five HCC cell lines were assessed by quantitative RT-PCR. We found that miR-139-5p was down-regulated in 89.7% of the HCC tissue samples and all of the HCC cell lines. In addition, luciferase reporter assays validated direct binding of miR-139-5p to the 3' untranslated region of zinc finger E-box binding homeobox 1 (ZEB1) and ZEB2. Ectopic expression of miR-139-5p suppressed and miR-139-in promoted EMT, migration, and invasion in Hep3B and SMMC7721 cells. Furthermore, over-expression of ZEB1 and ZEB2 ablated the inhibitory effects of miR-139-5p on migration and invasion in HCC cells. Our study indicates that miR-139-5p functions as a suppressor of HCC EMT and metastasis by targeting ZEB1 and ZEB2, and it may be a therapeutic target for metastatic HCC.
authors.affiliation: Department of General Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, China.
authors.forename: Gongcai
authors.initials: G
authors.lastname: Qiu
authors.affiliation: Department of General Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, China.
authors.forename: Yujia
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of General Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, China.
authors.forename: Haogang
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, China. Electronic address: wdq04510451@163.com.
authors.forename: Dequan
authors.initials: D
authors.lastname: Wu
mesh_terms: D020413:3' Untranslated Regions; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D000074165:Zinc Finger E-box Binding Homeobox 2; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: D020413:3' Untranslated Regions; D018398:Homeodomain Proteins; C555098:MIRN139 microRNA, human; D035683:MicroRNAs; D012097:Repressor Proteins; D014157:Transcription Factors; C486307:ZEB1 protein, human; C492363:ZEB2 protein, human; D000074165:Zinc Finger E-box Binding Homeobox 2; D000071799:Zinc Finger E-box-Binding Homeobox 1
keywords: Epithelial-mesenchymal transition (EMT); Hepatocellular carcinoma; Invasion; Metastasis; ZEB1/2; miR-139-5p