Epigenetic regulation of cancer biology and anti-tumor immunity by EZH2.
Epigenetic regulation of cancer biology and anti-tumor immunity by EZH2.
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DOI：
10.18632/oncotarget.12928
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发表时间：
2016-12-20
期刊：
影响因子：
--
通讯作者：
Boussiotis VA
中科院分区：
文献类型：
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作者：
Christofides A;Karantanos T;Bardhan K;Boussiotis VA
多梳蛋白调节染色质结构，在不同类型的细胞中对基因表达具有重要的调节作用。在哺乳动物细胞中发现了两个多梳复合体(多梳抑制复合体1(PRC1)和多梳抑制复合体2(PRC2))。PRC1和PRC2都紧凑染色质，也催化组蛋白修饰。组蛋白H3在赖氨酸27上发生甲基化，组蛋白H3在组蛋白H3上发生甲基化。组蛋白的这些改变可以通过调节染色质结构而导致基因表达模式的改变。大量研究强调了ZEST同源蛋白2的PRC2催化成分增强子(EZH2)在肿瘤发生发展中的作用，并在各种恶性肿瘤中发现了EZH2突变。EZH2通过调控关键基因的表达，积极参与细胞周期进程、细胞增殖、分化和凋亡等基本细胞过程。除了癌细胞外，EZH2在T效应细胞和T调节细胞的分化和功能中也起着决定性作用。本文综述了EZH2在人类恶性肿瘤中作用的最新研究进展，重点介绍了EZH2异常促进肿瘤发生的分子机制，并讨论了EZH2靶向通过激活直接抗癌机制和抗肿瘤免疫而发挥的抗肿瘤作用。
Polycomb group proteins regulate chromatin structure and have an important regulatory role on gene expression in various cell types. Two polycomb group complexes (Polycomb repressive complex 1 (PRC1) and 2 (PRC2)) have been identified in mammalian cells. Both PRC1 and PRC2 compact chromatin, and also catalyze histone modifications. PRC1 mediates monoubiquitination of histone H2A, whereas PRC2 catalyzes methylation of histone H3 on lysine 27. These alterations of histones can lead to altered gene expression patterns by regulating chromatin structure. Numerous studies have highlighted the role of the PRC2 catalytic component enhancer of zeste homolog 2 (EZH2) in neoplastic development and progression, and EZH2 mutations have been identified in various malignancies. Through modulating the expression of critical genes, EZH2 is actively involved in fundamental cellular processes such as cell cycle progression, cell proliferation, differentiation and apoptosis. In addition to cancer cells, EZH2 also has a decisive role in the differentiation and function of T effector and T regulatory cells. In this review we summarize the recent progress regarding the role of EZH2 in human malignancies, highlight the molecular mechanisms by which EZH2 aberrations promote the pathogenesis of cancer, and discuss the anti-tumor effects of EZH2 targeting via activating direct anti-cancer mechanisms and anti-tumor immunity.