YY1 promotes HDAC1 expression and decreases sensitivity of hepatocellular carcinoma cells to HDAC inhibitor

• DOI: 10.18632/oncotarget.17196
• Publication Date: 2017-04-18T19:10:30Z
• Authors: Sheng Dong; Xiang Ma; Zusen Wang; Bing Han; Hao Zou; Zehua Wu; Yunjin Zang; Likun Zhuang
• Keywords: Male; 0301 basic medicine; Mice, Inbred BALB C; Carcinoma, Hepatocellular; Cell Survival; Liver Neoplasms; Mice, Nude; Apoptosis; Histone Deacetylase 1; Middle Aged; Xenograft Model Antitumor Assays; 3. Good health; Gene Expression Regulation, Neoplastic; Histone Deacetylase Inhibitors; 03 medical and health sciences; RNAi Therapeutics; Animals; Humans; Female; RNA Interference; Promoter Regions, Genetic; Research Paper; Cell Proliferation; Protein Binding

YY1 is a DNA-binding transcription factor and reported to be involved in cancer progression. Histone deacetylase inhibitor (HDACi) could inhibit proliferation and promote apoptosis of Hepatocellular carcinoma (HCC) cells. However, it is unclear about the roles of YY1 in the sensitivity of HCC cells to HDACi. In this study, firstly, we identified two drug-response profiles to HDACi in HCC cell lines, while our results showed that HDAC1 expression was positively correlated with YY1 in HCC cell lines and primary tumor tissues. Secondly, YY1 decreased the sensitivity of HCC cells to HDACi in vitro and in vivo. Furthermore, we found that YY1 promoted HDAC1 expression by binding to its promoter, while HDAC1 in turn up-regulated the expression of YY1. In conclusion, our results showed that YY1 could reduce the sensitivity of HCC cells to HDACi and might be a potential therapeutic target in HCC.