中文摘要：

染色体调节因子zeste增强子同源物2（EZH2）是多梳抑制复合体2（PRC2）中的一个催化亚基,具有组蛋白H3K27甲基转移酶的功能。EZH2在肿瘤的发生发展中发挥极其重要的作用,由EZH2失调所引起的表观遗传改变和基因表达谱异常的现象在肿瘤中广泛存在。EZH2作为PRC2的催化亚基可促进组蛋白甲基化,增加染色质结构稳定性,发挥转录抑制作用;亦可通过PRC2非依赖的途径发挥转录激活作用,相应分子机制复杂,具有高度的组织特异性。目前已知的几种EZH2失调机制包括EZH2异常表达、EZH2功能获得性或缺失性突变、H3K27脱甲基酶UTX突变及复发性H3K27错义突变等。针对EZH2靶向药物的设计策略主要集中于研发干扰其甲基转移酶活性的小分子抑制剂,包括催化反应中甲基供体的竞争性抑制剂和干扰PRC2稳定性的抑制剂等。本文主要论述EZH2对肿瘤的表观遗传调控及靶向EZH2肿瘤治疗药物的研究进展。

英文摘要：

Enhancer of zeste homolog 2（EZH2）is the catalytic subunit of polycomb repressor complex 2（PRC2）,a complex that methylates lysine-27 of histone H3（H3K27）. PRC2 facilitates chromatin compaction and gene silencing by modulating the methylation of H3K27,which is thought to be the classical function of EZH2 in several types of cancer. In some other situations,EZH2 also acts as an activator of transcription in a PRC2-independent manner. EZH2 has been demonstrated to be extensively involved in the development and progression of cancer by inducing aberrant histone modification and gene transcription via aberrant EZH2 expression,functional mutation or other mechanisms which are very context-dependent. EZH2 inhibitors targeting the catalytic activity of EZH2 or the stability of PRC2 have been designed for cancer therapies and some of them have produced positive effects. This review focuses on the regulation of EZH2 on cancer epigenetics and the development of therapeutic drugs targeting EZH2.