中国科技核心期刊
CN:31-1600/Q
ISSN:1004-0374
“健康与疾病的免疫”国际学术研讨会通知      关于有网站冒充本刊网站的声明
《生命科学》 2015, 27(7): 876-882
EZH2:调节癌症发展的多重表观遗传因子
冯 浩,高兴春,沙保勇,景晓红*
(西安医学院基础医学研究所细胞生物学转化医学研究室, 西安 710021)
摘 要:果蝇zeste 基因增强子的人类同源物2 (enhancer of zeste homolog 2, EZH2) 是表观遗传调控因子多梳抑制复合体2 (polycomb repressive complex 2, PRC2) 的催化亚基,可催化组蛋白H3 第27 位的赖氨酸三甲基化并沉默靶基因转录,调控癌症进展及干细胞干性维持等多种生命活动。多项研究证明,EZH2 不仅具有经典的PRC2 依赖的转录抑制作用,还可通过非PRC2 依赖的方式激活靶基因转录,亦或通过其激活性或失活性的突变调节下游靶基因的活性。目前,已在多种癌细胞中检测到了EZH2 的过表达或突变,并且其变化与癌症的恶性程度密切相关。因此,靶向EZH2 及其介导的信号通路的研究将成为一个全新的癌症基因治疗的方向。
 
EZH2: a multi-faceted functional epigenetic regulator of cancer progression
FENG Hao, GAO Xing-Chun, SHA Bao-Yong , JING Xiao-Hong*
(Institute of Basic Medical Science, Xi’an Medical University, Xi’an 710021, China)
Abstact: Enhancer of zeste homolog 2 (EZH2) is a catalytic subunit of epigenetic regulator polycomb repressive complex 2 (PRC2), which trimethylates Lys 27 of histone H3, and leads to silence of the target genes that are involved in a variety of biological processes including tumor progression and stem cell maintenance. The accumulated evidence shows that, beside to its canonical PRC2-dependent transcriptional repression function, EZH2 also acts as a gene activator in a PRC2-independent manner, or regulates downstream gene activity through the activating mutations and inactivating mutations of EZH2 itself. Furthermore, overexpression and mutation of EZH2 have been detected in diverse cancers, and been associated with tumor malignancy. Therefore, targeting EZH2 and EZH2-mediated signaling pathway will provide us a novel targeted therapy for human cancer in the future.
 
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