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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 inmore » 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. - Highlights: • Sirt1 is a direct target of miR-133b in HCC. • miR-133b over-expression suppresses HCC progression in vitro and in vivo. • Sirt1 restoration reverses the effect of miR-133b over-expression on HCC cells. • GPC3 down-regulation reverses the effect of Sirt1 up-regulation on HCC cells. • Sirt1 activates Wnt β-catenin signaling by GPC3 in vitro.« less

Authors:
 [1];  [2]; ;  [1];  [3];  [2];  [1];  [4];  [5]
  1. School of Biomedicine, Chengdu Medical College, Chengdu, Sichuan 610500 (China)
  2. The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan 610041 (China)
  3. Laboratory Research Center, First Affiliated Hospital, Chongqing Medical University, Chongqing 400016 (China)
  4. (China)
  5. (United States)
Publication Date:
OSTI Identifier:
22648566
Resource Type:
Journal Article
Journal Name:
Experimental Cell Research
Additional Journal Information:
Journal Volume: 343; Journal Issue: 2; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0014-4827
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; APOPTOSIS; BORON CHLORIDES; BUILDUP; CELL PROLIFERATION; GENES; HEPATOMAS; IN VITRO; IN VIVO; INHIBITION; MESSENGER-RNA; ORIGIN; POTENTIALS; PROLIFERATION; REGULATIONS; SIGNALS; TRANSCRIPTION; TRANSCRIPTION FACTORS; TRANSLOCATION

Citation Formats

Tian, Zhijie, Jiang, Hequn, Liu, Ying, Huang, Yong, Xiong, Xin, Wu, Hongwei, E-mail: hongweiwu2118@sina.com, Dai, Xiaozhen, E-mail: xiaozhendai2012@163.com, Chongqing University, Key Laboratory of Biorheological Science and Technology, Ministry of Education, Chongqing 400044, and Department of Pediatrics, University of Louisville School of Medicine, Louisville, KY. MicroRNA-133b inhibits hepatocellular carcinoma cell progression by targeting Sirt1. United States: N. p., 2016. Web. doi:10.1016/J.YEXCR.2016.03.027.
Tian, Zhijie, Jiang, Hequn, Liu, Ying, Huang, Yong, Xiong, Xin, Wu, Hongwei, E-mail: hongweiwu2118@sina.com, Dai, Xiaozhen, E-mail: xiaozhendai2012@163.com, Chongqing University, Key Laboratory of Biorheological Science and Technology, Ministry of Education, Chongqing 400044, & Department of Pediatrics, University of Louisville School of Medicine, Louisville, KY. MicroRNA-133b inhibits hepatocellular carcinoma cell progression by targeting Sirt1. United States. doi:10.1016/J.YEXCR.2016.03.027.
Tian, Zhijie, Jiang, Hequn, Liu, Ying, Huang, Yong, Xiong, Xin, Wu, Hongwei, E-mail: hongweiwu2118@sina.com, Dai, Xiaozhen, E-mail: xiaozhendai2012@163.com, Chongqing University, Key Laboratory of Biorheological Science and Technology, Ministry of Education, Chongqing 400044, and Department of Pediatrics, University of Louisville School of Medicine, Louisville, KY. Sun . "MicroRNA-133b inhibits hepatocellular carcinoma cell progression by targeting Sirt1". United States. doi:10.1016/J.YEXCR.2016.03.027.
@article{osti_22648566,
title = {MicroRNA-133b inhibits hepatocellular carcinoma cell progression by targeting Sirt1},
author = {Tian, Zhijie and Jiang, Hequn and Liu, Ying and Huang, Yong and Xiong, Xin and Wu, Hongwei, E-mail: hongweiwu2118@sina.com and Dai, Xiaozhen, E-mail: xiaozhendai2012@163.com and Chongqing University, Key Laboratory of Biorheological Science and Technology, Ministry of Education, Chongqing 400044 and Department of Pediatrics, University of Louisville School of Medicine, Louisville, KY},
abstractNote = {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. - Highlights: • Sirt1 is a direct target of miR-133b in HCC. • miR-133b over-expression suppresses HCC progression in vitro and in vivo. • Sirt1 restoration reverses the effect of miR-133b over-expression on HCC cells. • GPC3 down-regulation reverses the effect of Sirt1 up-regulation on HCC cells. • Sirt1 activates Wnt β-catenin signaling by GPC3 in vitro.},
doi = {10.1016/J.YEXCR.2016.03.027},
journal = {Experimental Cell Research},
issn = {0014-4827},
number = 2,
volume = 343,
place = {United States},
year = {2016},
month = {5}
}