甲基转移酶EZH2在恶性肿瘤发生发展及治疗中的新进展

Research Progress of Methyltransferase EZH2 in the Pathogenesis and Treatment of Malignant Tumors

Zeste基因增强子同源物2(enhancer of Zeste homolog 2,EZH2)是一种重要的甲基转移酶,可作为核心催化亚基与其他成员形成多梳抑制复合物2,并通过调控转录活性进而促进肿瘤细胞的增殖、转移和耐药。EZH2在多种肿瘤组织中过表达或产生功能获得性突变,与肿瘤的发生发展及不良预后密切相关,可作为肿瘤治疗的有效靶点。目前,多种类型的EZH2抑制剂已用于肿瘤的基础和临床治疗研究,并取得里程碑式的成功。本文将对EZH2在肿瘤发生发展中的作用、分子机制和相关抑制剂的研究新进展进行综述。

Enhancer of zeste homolog 2(EZH2)is the catalytic subunit of the polycomb repressive complex 2(PRC2)that regulates downstream target gene expression,and promotes proliferation,metastasis and drug resistance of tumor cells.In many types of tumor,overexpressions and gain-of-function mutations of EZH2 correlate with the occurrence and development of tumors and poor prognosis.Therefore,EZH2 is a potential therapeutic target.Several inhibitors targeting EZH2 are in development,including basic research and clinical trials which have achieved a milestone.This article reviews the mechanism of EZH2,its role in tumorigenesis,and the new progress of EZH2-targeted inhibitors.