Increasing evidence has suggested that epigenetic and metabolic alterations in cancer cells are highly intertwined. As the master epigenetic regulator, enhancer of zeste homolog 2 (EZH2) suppresses gene transcription mainly by catalyzing the trimethylation of histone H3 at lysine 27 (H3K27me3) and exerts highly enzymatic activity in cancer cells. Cancer cells undergo the profound metabolic reprogramming and manifest the distinct metabolic profile. The emerging studies have explored that EZH2 is involved in altering the metabolic profiles of tumor cells by multiple pathways, which cover glucose, lipid, and amino acid metabolism. Meanwhile, the stability and methyltransferase activity of EZH2 can be also affected by the metabolic activity of tumor cells through various mechanisms, including post-translational modification. In this review, we have summarized the correlation between EZH2 and cellular metabolic activity during tumor progression and drug treatment. Finally, as a promising target, we proposed a novel strategy through a combination of EZH2 inhibitors with metabolic regulators for future cancer therapy.

中文翻译：

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表观遗传与代谢调控交响曲——组蛋白甲基转移酶EZH2与肿瘤代谢的相互作用。


越来越多的证据表明癌细胞的表观遗传和代谢改变是高度交织在一起的。作为主要的表观遗传调节因子，zeste 同源物增强子 2 (EZH2) 主要通过催化组蛋白 H3 在赖氨酸 27 (H3K27me3) 处的三甲基化来抑制基因转录，并​​在癌细胞中发挥高酶活性。癌细胞经历深刻的代谢重编程并表现出独特的代谢特征。新兴研究探索 EZH2 通过多种途径参与改变肿瘤细胞的代谢特征，其中包括葡萄糖、脂质和氨基酸代谢。同时，EZH2的稳定性和甲基转移酶活性也可以通过多种机制（包括翻译后修饰）受到肿瘤细胞代谢活性的影响。在这篇综述中，我们总结了肿瘤进展和药物治疗过程中EZH2与细胞代谢活性之间的相关性。最后，作为一个有希望的目标，我们提出了一种通过 EZH2 抑制剂与代谢调节剂相结合的新策略，用于未来的癌症治疗。