Li Long-Yuan
Graduate Institute of Cancer Biology, China Medical University, Taichung 404, Taichung, Taiwan ; Center for Molecular Medicine, China Medical University Hospital, Taichung 404, Taichung, Taiwan ; Department of Biotechnology, Asia University, Taichung 404, Taichung, Taiwan.
Biomedicine (Taipei). 2014;4(1):1. doi: 10.7603/s40681-014-0001-6. Epub 2014 Feb 12.
Enhancer of Zeste homlog 2 (EZH2) is a catalytic subunit of epigenetic regulator Polycomb repressive complex 2 (PRC2), which trimethylates Lys 27 of histone H3, leading to silencing of the target genes that are involved in a variety of biological processes including tumor progression and stem cell maintenance. However, in addition to its canonical PRC2-dependent transcriptional repression function, EZH2 also acts as a gene activator in a noncanonical PRC2-independent manner. Overexpression of EZH2 has been detected in diverse cancers, and is associated with tumor malignancy. Moreover, activating mutations and inactivating mutations of EZH2 are also associated with certain types of cancer. Given EZH2's multi-faceted function and role in cancer, context-specific strategy for targeting EZH2/EZH2-mediated signaling could serve as future targeted therapy/personalized medicine for human cancer.
锌指增强子同源物2（EZH2）是表观遗传调控因子多梳抑制复合物2（PRC2）的催化亚基，该复合物使组蛋白H3的赖氨酸27位点发生三甲基化，导致参与包括肿瘤进展和干细胞维持在内的多种生物学过程的靶基因沉默。然而，除了其经典的依赖PRC2的转录抑制功能外，EZH2还以非经典的不依赖PRC2的方式作为基因激活剂发挥作用。在多种癌症中均检测到EZH2的过表达，且其与肿瘤恶性程度相关。此外，EZH2的激活突变和失活突变也与某些类型的癌症有关。鉴于EZH2在癌症中的多方面功能和作用，针对EZH2/EZH2介导信号通路的特定背景策略有望成为未来人类癌症的靶向治疗/个性化药物。
