SIRT5 promotes cell proliferation and invasion in hepatocellular carcinoma by targeting E2F1

Chang,Liang; Xi,Liang; Liu,Yubin; Liu,Rui; Wu,Zhongshi; Jian,Zhixiang

doi:10.3892/mmr.2017.7875

SIRT5 promotes cell proliferation and invasion in hepatocellular carcinoma by targeting E2F1

Authors:
- Liang Chang
- Liang Xi
- Yubin Liu
- Rui Liu
- Zhongshi Wu
- Zhixiang Jian
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Affiliations: Southern Medical University, Guangzhou, Guangdong 510515, P.R. China, Department of Surgical Oncology, Inner Mongolia Baotou Steel General Hospital, Baotou, Inner Mongolia 404010, P.R. China, Department of General Surgery, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510000, P.R. China
Published online on: October 25, 2017 https://doi.org/10.3892/mmr.2017.7875
Pages: 342-349

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Abstract

Sirtuin 5 (SIRT5) is a member of the NAD+‑dependent class III protein deacetylases. Although it is known that SIRT5 deacetylates and activates urate oxidase in the liver mitochondria of mice, the mechanism of SIRT5 in the proliferation of hepatocellular carcinoma (HCC) remains to be fully elucidated. The present study investigated the expression and functional significance of SIRT5 in HCC, and examined the relevant mechanism. SIRT5 was found to be upregulated in HCC tissues and cell lines, and the higher expression of SIRT5 indicated poorer overall survival. Reverse transcription‑quantitative polymerase chain reaction analysis, western blot analysis, chromatin immunoprecipitation analysis, and luciferase reporter gene, proliferation and Transwell assays were performed to elucidate the function of SIRT5 in the regulation of cell proliferation and invasion in human HCC. Functionally, it was observed that the inhibition of SIRT5 significantly suppressed HCC cell proliferation and invasion, whereas the overexpression of SIRT5 promoted HCC cell proliferation and invasion in vitro. E2F transcription factor 1 (E2F1) was identified as a novel target gene of SIRT5. In addition, the knockdown of SIRT5 induced the expression of E2F1, and the knockdown of E2F1 in HCC cells partially reversed the effect of SIRT5 in promoting cell proliferation and invasion. Collectively, these data provide the first evidence, to the best of our knowledge, that the SIRT5 gene has an important regulatory role in liver carcinogenesis, and may function as a novel potential therapeutic target for HCC.

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