Molecular and Cell Biology Lab, Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai, China.
Molecular and Cell Biology Lab, Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai, China; Cullgen, Inc., 12671 High Bluff Drive, San Diego, CA 92130, USA.
Cell Rep. 2024 Oct 22;43(10):114815. doi: 10.1016/j.celrep.2024.114815. Epub 2024 Oct 4.
The catalytic activity of most epigenetic enzymes requires a metabolite produced by central carbon metabolism as a cofactor or (co-)substrate. The concentrations of these metabolites undergo dynamic changes in response to nutrient levels and environmental conditions, reprogramming metabolic processes and epigenetic landscapes. Abnormal accumulations of epigenetic modulatory metabolites resulting from mutations in metabolic enzymes contribute to tumorigenesis. In this review, we first present the concept that metabolite regulation of gene expression represents an evolutionarily conserved mechanism from prokaryotes to eukaryotes. We then review how individual metabolites affect epigenetic enzymes and cancer development. Lastly, we discuss the advancement of and opportunity for therapeutic targeting of metabolite-epigenetic regulation in cancer therapy.
大多数表观遗传酶的催化活性需要一种由中心碳代谢产生的代谢物作为辅助因子或（共）底物。这些代谢物的浓度会根据营养水平和环境条件发生动态变化，重新编程代谢过程和表观遗传景观。代谢酶突变导致的表观遗传调节代谢物的异常积累导致肿瘤发生。在这篇综述中，我们首先提出了这样一个概念，即代谢物对基因表达的调控代表了从原核生物到真核生物的一种进化保守机制。然后，我们回顾了单个代谢物如何影响表观遗传酶和癌症的发展。最后，我们讨论了在癌症治疗中靶向代谢物-表观遗传调控的治疗方法的进展和机会。
