组蛋白去乙酰化酶（HDACs）功能异常是肿瘤发生发展的重要原因之一，HDAC抑制剂的抗肿瘤作用已展示出一定的应用前景。然而，不同HDAC成员之间的相互调控对于肝癌形成的作用机制至今尚无研究论证，HDAC抑制剂在肝癌治疗中的疗效十分局限。我们的前期研究发现，肝细胞/肝癌细胞缺失HDAC1/2基因后，细胞增殖标记Ki67表达下调，有丝分裂期间姐妹染色单体不能正常对称分离，细胞增殖停滞；而肝脏特异敲除HDAC3基因后，小鼠肝细胞持续损伤并自发形成肝癌。HDAC1/2跟HDAC3的截然相反的功能提示它们之间可能存在拮抗作用。本研究拟用转基因小鼠和肝癌细胞株进行实验，通过免疫共沉淀以及染色质免疫共沉淀技术阐明HDAC1/2与HDAC3之间的相互作用关系及其在肝癌发生发展过程中的具体分子机制。本研究将丰富肿瘤发生机制理论，阐明HDAC抑制剂在肝癌治疗疗效局限的原因，为临床应用提供理论依据。

The dysfunction of histone deacetylases (HDACs), which are enzymes involve in epigenetic regulation, is one of the causes of tumor genesis. HDAC inhibitors (HDACi) have been shown to be a certain application prospect because of its anti-tumor effect. However, there is no report on the mechanism of the interaction between different HDAC members for the development of cancers, and the efficacy of HDACi in the treatment of liver cancer is very limited. In previous study, we found that hepatocytes or hepatoma carcinoma cell (HCC) which lack of HDAC1/2 showed downregulation of Ki67 ( a cell proliferation marker) and the sister chromatid can not normally separate during mitosis, and as a result the cells failed to proliferate. On the other hand, in the hepatocyte-specific HDAC3 gene deficient mice, the hepatocytes are progressively injured and loss the regenerative capacity and mice got HCC spontaneously. The opposite effect of HDAC1/2 and HDAC3 on HCC suggests that they may plays an antagonistic action. In this study, we plan to use transgenic mice and HCC strain as experimental subject, to demonstrate the of interaction between HDAC1/2 and HDAC3 in the development of HCC by Co-mmunoprecipitation (IP) and Chromatin immunoprecipitation (ChIP). Our study may help us understanding of mechanism of tumor genesis, and clarifying the reasons for the limitation of HDACi in the treatment of liver cancer, and providing theoretical basis for clinical application of HDACi.