N^(6)-甲基腺苷修饰在肿瘤程序性细胞死亡中的作用

Role of the N^(6)-methyladenosine modification in programmed cell death in tumors

非突变表观遗传重编程是肿瘤的关键特征之一,抵抗程序性细胞死亡是肿瘤的另一关键特征。作为体内最丰富的转录后表观遗传修饰方式,N^(6)-甲基腺苷(N^(6)-methyladenosine,m^(6)A)通过靶向调节程序性细胞死亡关键因子在肿瘤细胞凋亡、自噬、焦亡、铁死亡、坏死性凋亡、铜死亡中发挥重要作用。现已有靶向异常DNA甲基化、组蛋白修饰的表观遗传调节剂应用于临床,靶向m^(6)A修饰调控药物仍待探索。本文阐述了m^(6)A修饰调控肿瘤细胞程序性死亡的机制,旨在为通过调节m^(6)A修饰水平介导肿瘤细胞死亡这一潜在肿瘤治疗策略提供理论基础。

Non-mutational epigenetic reprogramming and resistance to programmed cell death are key characteristics of tumors.N^(6)-methyladenosine(m^(6)A)is the most abundant post-transcriptional epigenetic modification in vivo.It plays important roles in apoptosis,autophagy,pyroptosis,necroptosis,andiron(Fe)-induced(ferroptosis)and copper(Cu)-induced(cuproptosis)death of tumor cells by targeting and regulating the key factors of programmed cell death.Epigenetic modulators targeting aberrant DNA methylation and histone modification are being used in clinical applications;however,drugs specifically targeting m^(6)A modification regulation remain to be explored.In this review,the mechanisms of m^(6)A modification regulating tumor cell programmed death is discussed with the aim of providing a theoretical basis for mediating tumor cell death by regulating the level of m^(6)A modification as a potential tumor therapeutic strategy.