Regulation of chromosome regulator EZH2 in cancer epigenetics and EZH2 targeted drugs in cancer therapy / 中国药理学与毒理学杂志

ABSTRACT

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 chro?matin 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 acti?vator 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.