Salt-inducible kinase 2 functions as a tumor suppressor in hepatocellular carcinoma.

Abstract

Salt-inducible kinase 2 (SIK2) has been reported to be involved in cancer progression in a dichotomous manner. However, the role and mechanism of action of SIK2 in hepatocellular carcinoma (HCC) progression remain elusive. SIK2 expression in HCC tissues in The Cancer Genome Atlas (TCGA) database was analyzed using the AIPuFu platform. SIK2 expression in HCC cells was examined by quantitative real-time PCR and western blot analysis. The expression of N-cadherin, E-cadherin, β-catenin, and c-Myc was detected by western blot analysis. SIK2 was downregulated in HCC tissues compared with normal patients, and low SIK2 expression was correlated with poor prognosis in HCC patients in TCGA database. SIK2 was lowly expressed in HCC cells than that in normal human liver epithelial cells. SIK2 overexpression inhibited cell proliferation and invasion and promoted apoptosis in HCC cells, while SIK2 silencing exerted the opposite effects. Additionally, SIK2 overexpression inactivated the Wnt/β-catenin pathway in HCC cells, as evidenced by the reduced expression of β-catenin and c-Myc. β-catenin overexpression rescued the inhibitory effects of SIK2 on the malignant properties of HCC cells. Xenograft tumor experiment confirmed that SIK2 suppressed the growth of HCC cells in vivo. In conclusion, SIK2 exerted anti-tumor activity in HCC via inactivating the Wnt/β-catenin signaling pathway.