Overexpression of SIRT6 attenuates the tumorigenicity of hepatocellular carcinoma cells.

Haiyu Wang,Li Li,Jiangmin Li,Yadong Wang,Ding Zhang,Teng Pan,Haiyan Yang

doi:10.18632/oncotarget.19297

Abstract

ObjectiveThis study aimed to explore the effects of overexpression of sirtuin 6 (SIRT6) on the tumorigenicity of hepatocellular carcinoma (HCC) cellsMethodsStable SIRT6-overexpressed HCC cell lines were established by transfecting SIRT6 plasmid. Soft agar assay and tumor xenograft assay in nude mice were applied. Flow cytometry was employed to detect cell cycle distribution. Western blotting analysis was used to detect the expression of proteins.ResultsOverexpression of SIRT6 attenuated HepG2 and HCCLM3 cells proliferation, colony formation in vitro and tumor formation in nude mice, and resulted in the G1 phase cell cycle arrest. Overexpression of SIRT6 reduced the expression of cyclin D1 and p-ERK proteins in both HepG2 and HCCLM3 cells.ConclusionOverexpression of SIRT6 attenuates the tumorigenicity of HCC cells.

Highlights

Sirtuin 6 (SIRT6) is a member of the mammalian sirtuins family, which functions as a mono-ADPribosyltransferase and NAD+-dependent deacylase of both acetyl groups and long-chain fatty acyl groups [1]
Overexpression of SIRT6 reduced the expression of cyclin D1 and p-extracellular signal-regulated kinase (ERK) proteins in both HepG2 and HCCLM3 cells
Overexpression of SIRT6 attenuates the tumorigenicity of hepatocellular carcinoma (HCC) cells

Summary

Introduction

Sirtuin 6 (SIRT6) is a member of the mammalian sirtuins family, which functions as a mono-ADPribosyltransferase and NAD+-dependent deacylase of both acetyl groups and long-chain fatty acyl groups [1]. A number of studies have identified SIRT6 as a key regulator of hepatocellular carcinoma (HCC), but the functional roles of SIRT6 in liver cancer are inconsistent. Marquardt et al reported that loss of SIRT6 induced epigenetic changes which might be relevant to HCC development. Zhang et al reported that overexpression of SIRT6 suppressed HCC cell proliferation and induced apoptosis [16]. Additional two studies [17, 18] suggested that SIRT6 acted as an oncogene in HCC development. Their results showed that SIRT6 was upregulated in a subset of HCC tissues and SIRT6 knockdown by shRNA suppressed the growth of HCC cells, induced apoptosis, and inhibited tumor growth of HCC cells in vivo. Two stable SIRT6-overexpressed HCC cell lines were established to investigate the effects of overexpression of SIRT6 on HCC cell proliferation, cell cycle distribution, tumorigenicity in vitro and in vivo, and its related molecular mechanisms

Methods

Results

Conclusion