title: MicroRNA-133b inhibits hepatocellular carcinoma cell progression by targeting Sirt1.
abstract: MicroRNAs (miRNAs) are a class of small non-coding RNAs that function as critical gene regulators by targeting mRNAs for translational repression or degradation. In this study, we showed that the expression level of miR-133b was decreased, while Sirt1 mRNA expression levels were increased in hepatocellular carcinoma (HCC) and cell lines, and we identified Sirt1 as a novel direct target of miR-133b. The over-expression of miR-133b suppressed Sirt1 expression. In addition, miR-133b over-expression resulted in attenuating HCC cell proliferation and invasion together with apoptosis increase in vitro. HepG2 cell transplantation revealed that up-regulation of miR-133b could inhibit HCC tumor genesis in vivo. Forced expression of Sirt1 partly rescued the effect of miR-133b in vitro. Furthermore, our study showed that miR-133b over-expression or Sirt1 down-regulation elevated E-cadherin expression, and repressed glypican-3 (GPC3) and the anti-apoptotic proteins (Bcl-2, Bcl-xL, and Mcl-1) expression. The inhibition of GPC3 expression repressed Bcl-2, Bcl-xL, and Mcl-1 expression, and elevated E-cadherin expression. Moreover, the Sirt1 up-regulation resulted in increases in HCC cell proliferation and invasion together with decreases apoptosis, and increases in the cytosolic accumulation and nuclear translocation of the transcription factor β-catenin in vitro. But the effect of Sirt1 up-regulation was partly reversed by GPC3 down-regulation in vitro. Taken together, these findings provide insight into the role and mechanism of miR-133b in regulating HCC cell proliferation, invasion and apoptosis via the miR-133b/Sirt1/GPC3/Wnt β-catenin axis, and miR-133b may serve as a potential therapeutic target in HCC in the future.
authors.affiliation: School of Biomedicine, Chengdu Medical College, Chengdu, Sichuan 610500, China.
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Tian
authors.affiliation: The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan 610041, China.
authors.forename: Hequn
authors.initials: H
authors.lastname: Jiang
authors.affiliation: School of Biomedicine, Chengdu Medical College, Chengdu, Sichuan 610500, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: School of Biomedicine, Chengdu Medical College, Chengdu, Sichuan 610500, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Laboratory Research Center, First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Xiong
authors.affiliation: The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan 610041, China. Electronic address: hongweiwu2118@sina.com.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Wu
authors.affiliation: School of Biomedicine, Chengdu Medical College, Chengdu, Sichuan 610500, China; Chongqing University, Key Laboratory of Biorheological Science and Technology, Ministry of Education, Chongqing 400044, China; Department of Pediatrics, University of Louisville School of Medicine, Louisville, KY, USA. Electronic address: xiaozhendai2012@163.com.
authors.forename: Xiaozhen
authors.initials: X
authors.lastname: Dai
mesh_terms: D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D015536:Down-Regulation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D053673:Glypicans / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology*; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D056564:Sirtuin 1 / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics; D060449:Wnt Signaling Pathway
chemical_list: C105937:GPC3 protein, human; D053673:Glypicans; C548234:MIRN133 microRNA, human; D035683:MicroRNAs; D056564:Sirtuin 1
keywords: Apoptosis; Hepatocellular carcinoma; MiR-133b; Proliferation; Sirt1