EZH2 is the catalytic subunit of the polycomb repressive complex 2 (PRC2), which along with other PRC2 components mediates gene expression suppression via the methylation of Histone H3 at lysine 27. Recent studies have revealed a dichotomous role of EZH2 in physiology and in the pathogenesis of cancer. While it plays an essential role in the development of the lymphoid system, its deregulation, whether due to genetic or non-genetic causes, promotes B cell- and T cell-related lymphoma or leukemia. These findings triggered a boom in the development of therapeutic EZH2 inhibitors in recent years. Here, we discuss physiologic and pathogenic function of EZH2 in lymphoid context, various internal causes of EZH2 aberrance and how EZH2 modulates lymphomagenesis through epigenetic silencing, post-translational modifications (PTMs), orchestrating with surrounding tumor micro-environment and associating with RNA or viral partners. We also summarize different strategies to directly inhibit PRC2-EZH2 or to intervene EZH2 upstream signaling.

中文翻译：

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EZH2淋巴恶性肿瘤的异常：潜在的机制和治疗意义。

EZH2是多梳抑制复合物2（PRC2）的催化亚基，它与其他PRC2组分通过组蛋白H3在赖氨酸27处的甲基化介导基因表达抑制。最近的研究表明EZH2在生理学和发病机理中具有二分作用。癌症。尽管它在淋巴系统的发育中起着至关重要的作用，但由于遗传或非遗传原因，其失调会促进与B细胞和T细胞相关的淋巴瘤或白血病。这些发现引发了近年来治疗性EZH2抑制剂的发展热潮。在这里，我们讨论了EZH2在淋巴样环境中的生理和致病功能，EZH2异常的各种内部原因以及EZH2如何通过表观遗传沉默，翻译后修饰（PTM）调节淋巴瘤的发生，与周围的肿瘤微环境协调，并与RNA或病毒伴侣相关联。我们还总结了直接抑制PRC2-EZH2或干预EZH2上游信号的不同策略。