期刊
EXPERIMENTAL CELL RESEARCH
卷 343, 期 2, 页码 135-147出版社
ELSEVIER INC
DOI: 10.1016/j.yexcr.2016.03.027
关键词
miR-133b; Sirt1; Hepatocellular carcinoma; Proliferation; Apoptosis
资金
- National Natural Science Foundation of China [81200917]
- Sichuan Provincial Education Department [11ZA205]
- Visiting Scholar Foundation of Key Laboratory of Biorheological Science and Technology (Chongqing University) [CQKLBST-2012-003]
- Scientific Research Fund of Health and Family Planning Commission of Sichuan Province [130297, 150048]
- Ministry of Education and Higher Education Quality Engineering, Sichuan province
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 GPO 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 beta-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 beta-catenin axis, and miR-133b may serve as a potential therapeutic target in HCC in the future. (c) 2016 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据