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

Sheng Dong,Bing Han,Xiang Ma,Zehua Wu,Likun Zhuang,Hao Zou,Zusen Wang,Yunjin Zang

doi:10.18632/oncotarget.17196

Sheng Dong, Bing Han + Show 6 more

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https://doi.org/10.18632/oncotarget.17196

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Journal: Oncotarget	Publication Date: Apr 18, 2017
Citations: 20	License type: cc-by

Affiliation: Affiliated Hospital of Qingdao University

Abstract

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.

Highlights

Hepatocellular carcinoma (HCC) is one of the most common and malignant tumors in the world
In order to explore the effects of Histone deacetylase inhibitor (HDACi) on different HCC cell lines, firstly we evaluated the sensitivity of HCC cell lines to non-specific HDACis SAHA and TSA by calculating IC50 values (Figure 1A)
Our results showed that Yin-Yang 1 (YY1) level was higher in high-dose sensitive HCC cells and exhibited a positive correlation with HDAC1 in HCC cell lines (Figure 2D and 2E)

Summary

Introduction

Hepatocellular carcinoma (HCC) is one of the most common and malignant tumors in the world. The majority of HCC patients are diagnosed at an advanced stage and conventional chemotherapy is usually ineffective. The mortality rate of HCC is still very high [1]. In the past few years, more and more studies showed that the molecular targeting therapy provided an opportunity for the treatment of patients with cancers including HCC. Sorafenib, a multikinase inhibitor, is one of the molecular targeted drugs in treating patients with advanced HCC [2]. The median life expectancy of HCC patients extended by Sorafenib was not long and many patients developed acquired resistance to sorafenib [3]. It is necessary to develop a novel molecular targeting therapy for HCC

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Conclusion