Inactivation of Wnt/β‐catenin signaling pathway by SIRT 6 inhibits tumor growth and proliferation in hepatocellular carcinoma

Abstract

Sirtuins are a family of NAD+‐dependent protein involved in regulating the lifespan and metabolic homeostasis. Sirtuin 6 (SIRT6) has been reported to have tumor suppressing effect in liver. However, the precise molecular mechanism of SIRT6 in human hepatocellular carcinoma (HCC) has not been clearly understood. Therefore, we have investigated the importance of SIRT6 function in HCC cell lines, HepG2 and SNU449. SIRT6 was highly expressed in human HCC cells. Overexpression of SIRT6 significantly diminished the viability of HCC cells whereas silencing of SIRT6 stimulated the viability of HCC cells. Overexpression of SIRT6 increased expression of cleaved‐PARP and cleaved‐caspase9 and decreased the PARP, caspase9, and caspase3. Knockdown of SIRT6 increased the number and size 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 in a time dependent manner. Moreover, overexpression of SIRT6 inhibited vimentin, UPA, and MMP9 protein levels while silencing of SIRT6 in HCC cells increased the protein levels of vimentin, UPA, and MMP9. P‐β‐catenin levels was increased by overexpression of SIRT6 and was decreased by silencing of SIRT6. These data suggest that SIRT6 inhibits the proliferation, invasion and metastasis of HCC cells and may play as a tumor suppressor in HCC cells.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.