J Cancer 2019; 10(16):3871-3882. doi:10.7150/jca.31266

Research Paper

SIRT5 Promotes Hepatocellular Carcinoma Progression by Regulating Mitochondrial Apoptosis

Rixin Zhang1*, Chengye Wang1*, Yu Tian1,2, Yifan Yao1, Jiakai Mao1, Haibo Wang1, Zhenghan Li1, Yakun Xu1, Mingliang Ye3, Liming Wang1✉

1. Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The Second Hospital of Dalian Medical University, NO.467, Zhongshan Road, Dalian, Liaoning 116023, China.
2. Department of Vascular Surgery, The Second Hospital of Dalian Medical University, NO.467, Zhongshan Road, Dalian, Liaoning 116023, China.
3. CAS Key Lab of Separation Sciences for Analytical Chemistry, National Chromatographic Research and Analysis Center, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, NO.457, Zhongshan Road, Dalian, Liaoning 116023, China.
*These authors have contributed equally to this work.

Abstract

SIRT5 belongs to a family of NAD+-dependent lysine deacetylases called sirtuins. Although accumulating evidence indicates SIRT5 upregulation in cancers, including liver cancer, the detailed roles and mechanisms remain to be revealed. Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths among men worldwide, and finding effective targets for HCC treatment and prevention is urgently needed. In the present study, we confirmed that mitochondrial sirtuins, particularly SIRT5, are more highly expressed in HCC cell lines than in normal liver cell lines. Moreover, SIRT5 knockdown suppresses HCC cell proliferation and SIRT5 overexpression promotes HCC cell proliferation. Furthermore, we verified that SIRT5 knockdown increases HCC cell apoptosis via the mitochondrial pathway. By co-IP and western blotting, we illustrated that SIRT5 deacetylates cytochrome c thus regulating HCC cell apoptosis. Taken together, our findings suggest that SIRT5 may function as a prognostic factor and drug target for HCC treatment.

Keywords: SIRT5, HCC, Cytochrome c, Acetylation

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How to cite this article:
Zhang R, Wang C, Tian Y, Yao Y, Mao J, Wang H, Li Z, Xu Y, Ye M, Wang L. SIRT5 Promotes Hepatocellular Carcinoma Progression by Regulating Mitochondrial Apoptosis. J Cancer 2019; 10(16):3871-3882. doi:10.7150/jca.31266. Available from http://www.jcancer.org/v10p3871.htm