SIRT6 regulates the proliferation and apoptosis of hepatocellular carcinoma via the ERK1/2 signaling pathway

Abstract

Hepatocellular carcinoma (HCC) is the most common type of liver cancer, and exhibits a high mortality rate. Sirtuin (SIRT)6 is a member of the sirtuin family, which may be useful targets in the treatment of tumors. The present study aimed to explore the expression of SIRT6 in numerous HCC cell lines and investigate the role of SIRT6 in the proliferation and apoptosis of the HCC cells, and the underlying mechanisms. Overexpression and silencing of SIRT6 were performed by transfection of Huh-7 cells with synthetic overexpression and small interfering RNA (siRNA) plasmids. Cell proliferation was evaluated using a Cell Counting Kit-8 assay. The apoptosis rate was measured via flow cytometry. Cloning efficiency was assessed using plate clone formation assays. The expression of mRNAs and proteins were determined via reverse transcription-quantitative PCR and western blot analyses, respectively. SIRT6 was overexpressed in Hep3B, Huh-7, MHCC-97H, MHCC-97L, MHCC-LM6, MHCC-LM3, YY-8103 and SK-hep-1 cell lines, compared with MIHA and HL-7702 normal liver cell lines. Overexpression of SIRT6 increased the proliferation of Huh-7 cells, upregulated the expression of Bcl-2 and phosphorylation of extracellular-signal regulated protein kinase (ERK), and decreased the expression of cleaved-caspase-3 and Bcl-2-associated X protein (Bax) in Huh-7 cells. siRNA-mediated silencing of SIRT6 decreased the proliferation and increased the apoptosis of Huh-7 cells, downregulated the expression of Bcl-2 and phosphorylated-ERK, and promoted the expression of cleaved-caspase-3 and Bax. The proliferation of Huh-7 cells was decreased using the ERK1/2 inhibitor U0126. The results suggested that SIRT6 affected the proliferation and apoptosis of HCC cells via the regulation of the ERK1/2 pathway, altering the activation of the intrinsic apoptosis pathway. SIRT6 may be a potential target for the treatment of HCC; however, its role requires further investigation.