Symphony of epigenetic and metabolic regulation—interaction between the histone methyltransferase EZH2 and metabolism of tumor
Symphony of epigenetic and metabolic regulation—interaction between the histone methyltransferase EZH2 and metabolism of tumor
复制标题
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
DOI：
10.1186/s13148-020-00862-0
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发表时间：
2020
影响因子：
5.7
通讯作者：
Lixiang Xue
中科院分区：
文献类型：
--
作者：
Tengrui Zhang;Yueqing Gong;Hui Meng;Chen Li;Lixiang Xue
越来越多的证据表明，癌细胞中的表观遗传和代谢改变是高度交织在一起的。作为表观遗传调控的主要因子，EZH2主要通过催化组蛋白H3在赖氨酸27位的三甲基化（H3K27me3）来抑制基因转录，并在癌细胞中发挥高度的酶活性。癌细胞经历深刻的代谢重编程，并表现出独特的代谢谱。新兴的研究已经探索了EZH2通过多种途径参与改变肿瘤细胞的代谢谱，这些途径包括葡萄糖、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受到肿瘤细胞代谢活性的影响，包括翻译后修饰。本文就EZH2与肿瘤进展及药物治疗过程中细胞代谢活性的相关性进行综述。最后，作为一个有前途的目标，我们提出了一种新的策略，通过EZH2抑制剂与代谢调节剂的组合，用于未来的癌症治疗。
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.