Dong Sheng, Ma Xiang, Wang Zusen, Han Bing, Zou Hao, Wu Zehua, Zang Yunjin, Zhuang Likun
Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China.
Institute of Transplantation Science, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China.
Oncotarget. 2017 Jun 20;8(25):40583-40593. doi: 10.18632/oncotarget.17196.
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.
YY1是一种DNA结合转录因子，据报道其参与癌症进展。组蛋白去乙酰化酶抑制剂（HDACi）可抑制肝癌（HCC）细胞的增殖并促进其凋亡。然而，YY1在HCC细胞对HDACi敏感性中的作用尚不清楚。在本研究中，首先，我们在HCC细胞系中鉴定出两种对HDACi的药物反应谱，而我们的结果表明HDAC1表达在HCC细胞系和原发性肿瘤组织中与YY1呈正相关。其次，YY1在体外和体内均降低了HCC细胞对HDACi的敏感性。此外，我们发现YY1通过结合HDAC1启动子促进其表达，而HDAC1反过来上调YY1的表达。总之，我们的结果表明YY1可降低HCC细胞对HDACi的敏感性，可能是HCC的一个潜在治疗靶点。
