Introduction: Despite SIRT6 has been reported to express in variety cancers and to regulate in tumorigenesis, the functional role of sirtuin6 in human cancers remain unknown. To investigate the biological mechanism of SIRT6 in hepatocellular carcinoma (HCC), we have studied the importance of SIRT6 function in HCC cell lines, HepG2 and SNU449.
Methods: We performed MTT assay, colony formation assay, western blotting, wound healing assay, matregel transwell study, overexpression of SIRT6, and knockdown of SIRT6 in human HCC cell lines HepG2 and SNU449.
Results: SIRT6 was highly expressed in human HCC cells. Overexpression of SIRT6 significantly diminished the viability of HCC cells whereas silencing of sirtuin6 stimulated the viability of HCC cells. Overexpression of SIRT6 increased expression of cleaved-caspase-9 and cleaved-PARP and decreased the numbers of colonies. In addition, overexpression of SIRT6 significantly inhibited the invasion and metastasis of HCC cells whereas silencing of SIRT6 increased the invasion and metastasis abilities of HCC cells with time dependent manner. Moreover, overexpression of SIRT6 inhibited vimentin, β-catenin, and UPA protein levels while silencing of SIRT6 in HCC cells induced increase the protein levels of UPA, vimentin, and twist. P-β-catenin levels was increased by overexpression of SIRT6 and was decreased by silencing of SIRT6.
Conclusion: In conclusion, SIRT6 inhibited the proliferation and invasion of HCC cells and may plays as a tumor suppressor in HCC cells.