重庆医科大学病毒性肝炎研究所

Institute for Viral Hepatitis,Chongqing Medical University


暨感染性疾病分子生物学教育部重点实验室

Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education


陈娟研究员团队发表Sirtuin 3 inhibits hepatocellular carcinoma growth through the glycogen synthase kinase-3β/BCL2-associated X protein-dependent apoptotic pathway.
发布时间:2017-09-14 16:10:34

Sirtuin 3 inhibits hepatocellular carcinoma growth through the glycogen synthase kinase-3β/BCL2-associated X protein-dependent apoptotic pathway.

Song CL1Tang H1Ran LK1Ko BC2,3Zhang ZZ4Chen X1Ren JH1Tao NN1Li WY1Huang AL1,5Chen J1.

Oncogene. 2016 Feb 4;35(5):631-41. doi: 10.1038/onc.2015.121. Epub 2015 Apr 27.

PMID:25915842       DOI:10.1038/onc.2015.121


Abstract

SIRT3 is a class III histone deacetylase that has been implicated in a variety of cancers. The role of SIRT3 in hepatocellular carcinoma (HCC) remains elusive. In this study, we found that SIRT3 expression was frequently repressed in HCC and its downregulation was closely associated with tumor grade and size. Ectopic expression of SIRT3 inhibited cell growth and induced apoptosis in HCC cells, whereas depletion of SIRT3 in immortalized hepatocyte promoted cell growth and decreased epirubicin-induced apoptosis. Mechanistic studies revealed that SIRT3 deacetylated and activated glycogen synthase kinase-3β (GSK-3β), which subsequently induced expression and mitochondrial translocation of the pro-apoptotic protein BCL2-associated X protein (Bax) to promote apoptosis. GSK-3β inhibitor or gene silencing of BAX reversed SIRT3-induced growth inhibition and apoptosis. Furthermore, SIRT3 overexpression also suppressed tumor growth in vivo. Together, this study reveals a role of SIRT3/GSK-3β/Bax signaling pathway in the suppression of HCC growth, and also suggests that targeting this pathway may represent a potential therapeutic approach for HCC treatment.



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