EZH2在肿瘤中的作用及其抑制剂的研究进展  

Research advances in role of EZH2 in tumors and its inhibitors

作　　者：顾馨集 黄韵晓 于兵 GU Xinji;HUANG Yunxiao;YU Bing(School of Basic Medicine,Naval Military Medical University,Shanghai 200433,China;Department of Cell Biology,School of Basic Medicine,Naval Medical University,Shanghai 200433,China)

机构地区：[1]海军军医大学基础医学院,上海200433 [2]海军军医大学基础医学院细胞生物学教研室,上海200433

出　　处：《解放军医学院学报》2024年第7期811-816,F0003,共7页Academic Journal of Chinese PLA Medical School

基　　金：国家自然科学基金项目(82173369)。

摘　　要：Zeste增强子同源物2(enhancer of zeste homolog 2,EZH2)的高表达与肿瘤发生、发展、浸润、转移和临床不良预后密切相关。EZH2通过多梳抑制复合体2(polycomb inhibition complex 2,PRC2)依赖的H3K27甲基化或非组蛋白甲基化、不依赖PRC2的非组蛋白甲基化、直接的蛋白-蛋白相互作用等多种机制激活下游基因,在肿瘤相关基因的转录抑制和肿瘤发生发展调控中起着至关重要的作用。因此,EZH2被认为是一个很有前景的肿瘤治疗靶点。目前,针对EZH2的小分子抑制剂的开发和临床试验已成为一个突出的研究领域。本文综述了EZH2的功能及其调控机制,并重点介绍了热点抑制剂的最新进展,旨在为EZH2及其抑制剂的进一步研究和应用于各种癌症治疗提供参考。The overexpression of of Zeste enhancer homolog 2(EZH2)is closely associated with tumor initiation,progression,invasion,metastasis,and unfavorable clinical prognosis.EZH2 plays a crucial role in the transcriptional repression of tumor-related genes and the regulation of tumorigenesis and development through various mechanisms,including PRC2-dependent H3K27 methylation or non-histone methylation,PRC2-independent non-histone methylation,direct protein-protein interactions,etc,to activate downstream genes.Therefore,EZH2 is considered to be a promising therapeutic target for tumor treatment.Currently,the development and clinical trials of small molecule inhibitors targeting EZH2 have emerged as a prominent area of research.This article reviews functions and regulatory mechanisms of EZH2 and highlights recent advancements in hotspot inhibitors,aiming to provide valuable insights for further research and application in diverse cancer treatments.

关 键 词：Zeste增强子同源物2 EZH2抑制剂 肿瘤 H3K27me3 表观遗传 

分 类 号：R730.53[医药卫生—肿瘤]