Overexpression of HDAC6 suppresses tumor cell proliferation and metastasis by inhibition of the canonical Wnt/β-catenin signaling pathway in hepatocellular carcinoma.

Abstract

Histone deacetylase 6 (HDAC6), a specific histone deacetylase family member, serves an essential role in the regulation of gene expression, cell cycle progression, autophagy and apoptosis. There are numerous reports on the function of HDAC6 in cancer. However, the specific function of HDAC6 in hepatocellular carcinoma (HCC) has yet to be revealed. In the present study, the expression of HDAC6 was revealed to be downregulated in human HCC cell lines and tissues. The aberrant activation of the canonical Wnt/β-catenin signaling pathway was revealed to be involved in hepatocarcinogenesis and metastasis. It was additionally revealed that the overexpression of HDAC6 decreased the expression of β-catenin protein levels which attenuated the canonical Wnt/β-catenin signaling pathway and suppressed the proliferation of HCC cells. In addition, the upregulation of HDAC6 inhibited the epithelial-to-mesenchymal transition in HCC by increasing the E-cadherin protein levels and decreasing the N-cadherin, vimentin and matrix metalloproteinase-9 protein levels. Furthermore, HDAC6 also exerted an effect on the cell cycle arrest and the induction of apoptosis. These results demonstrated that HDAC6 functioned as a tumor suppressor in HCC by attenuating the activity of the canonical Wnt/β-catenin signaling pathway. Therefore, HDAC6 may serve as a potential therapeutic target for the treatment of HCC.