School of Medicine,Tsinghua University,Beijing 100084,China.
Zhejiang Da Xue Xue Bao Yi Xue Ban. 2021 Feb 25;50(1):1-16. doi: 10.3724/zdxbyxb-2021-0053.
Epigenetics concerns gene regulatory mechanisms beyond DNA sequence,such as DNA methylation,histone modification,chromatin remodeling,and non-coding RNA. Epigenetic mechanisms play a key role in development,cell fate decision and tumorigenesis. Chromatin modifications and its high order structure across our genome are major forms of epigenetic information,and its establishment and maintenance are closely related to cell metabolism. Metabolic changes in cancer cells include aerobic glycolysis,increased glucose uptake,abnormally active glutamine metabolism,and the use of non-conventional energy supply. These changes meet the vigorous energy and matter needs for the development and spread of cancer,and help tumor cells adapt to hypoxia microenvironment for their survival,proliferation,invasion and migration. There is a complex relationship between epigenetic modifications and cell metabolism in tumor. On the one hand,metabolites in tumor cells may act as cofactors,modification donors or antagonists of epigenetic enzymes,thus modulating the epigenetic landscape. On the other hand,epigenetic modifications can directly regulate the expression of metabolic enzymes,transporters,signaling pathway and transcription factors to affect cell metabolism. This article reviews the crosstalk between epigenetics and cancer metabolism,to explore their potential future applications in the treatment of tumors.
表观遗传学关注的是超越 DNA 序列的基因调控机制,如 DNA 甲基化、组蛋白修饰、染色质重塑和非编码 RNA。表观遗传机制在发育、细胞命运决定和肿瘤发生中起着关键作用。染色质修饰及其在我们基因组中的高级结构是表观遗传信息的主要形式,其建立和维持与细胞代谢密切相关。癌细胞中的代谢变化包括有氧糖酵解、增加葡萄糖摄取、异常活跃的谷氨酰胺代谢以及非常规能量供应的利用。这些变化满足了癌症发展和扩散所需的旺盛能量和物质需求,并帮助肿瘤细胞适应缺氧微环境以生存、增殖、侵袭和迁移。在肿瘤中,表观遗传修饰和细胞代谢之间存在着复杂的关系。一方面,肿瘤细胞中的代谢物可能作为表观遗传酶的辅助因子、修饰供体或拮抗剂,从而调节表观遗传景观。另一方面,表观遗传修饰可以直接调节代谢酶、转运蛋白、信号通路和转录因子的表达,从而影响细胞代谢。本文综述了表观遗传学与癌症代谢之间的相互作用,探讨了它们在肿瘤治疗中的潜在未来应用。