NHC Key Laboratory of Carcinogenesis, Hunan Key Laboratory of Oncotarget Gene, the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/ Hunan Cancer Hospital, Changsha, China.
Xiangya School of Medicine, Central South University, Changsha, China.
Cell Death Dis. 2024 Oct 28;15(10):783. doi: 10.1038/s41419-024-07148-w.
N-Methyladenosine (mA) is an evolutionarily highly conserved epigenetic modification that affects eukaryotic RNAs, especially mRNAs, and mA modification is commonly linked to tumor proliferation, progression, and therapeutic resistance by participating in RNA metabolism. Autophagy is an intracellular degradation and recycling biological process by which cells remove damaged organelles, protein aggregates, and other intracellular wastes, and release nutrients to maintain cell survival when energy is scarce. Recent studies have shown that mA modification plays a critical role in the regulation of autophagy, affecting the initiation of autophagy, the formation and assembly of autophagosomes, and lysosomal function by regulating critical regulatory molecules involved in the process of autophagy. Moreover, autophagy can also affect the expression of the three types of regulators related to mA, which in turn affects the levels of their target genes via mA modification. Thus, mA modification and autophagy form a sophisticated regulatory network through mutual regulation, which plays an important role in tumor progression and therapeutic resistance. In this manuscript, we reviewed the effects of mA modification on autophagy as well as the effects of autophagy on mA modification and the roles of the mA-autophagy axis in tumor progression and therapy resistance. Additionally, we summarized the value and application prospects of key molecules in the mA-autophagy axis in tumor diagnosis and therapy.
N6-甲基腺苷（m6A）是一种进化上高度保守的表观遗传修饰，影响真核 RNA，特别是 mRNAs，m6A 修饰通常通过参与 RNA 代谢与肿瘤增殖、进展和治疗抵抗有关。自噬是一种细胞内降解和回收的生物过程，通过该过程，细胞可以去除受损的细胞器、蛋白质聚集体和其他细胞内废物，并在能量匮乏时释放营养物质以维持细胞存活。最近的研究表明，m6A 修饰在自噬的调控中发挥着关键作用，通过调节自噬过程中涉及的关键调节分子，影响自噬的起始、自噬体的形成和组装以及溶酶体功能。此外，自噬还可以影响与 m6A 相关的三种调节因子的表达，进而通过 m6A 修饰影响其靶基因的水平。因此，m6A 修饰和自噬通过相互调节形成一个复杂的调控网络，在肿瘤进展和治疗抵抗中发挥着重要作用。在本文中，我们综述了 m6A 修饰对自噬的影响，以及自噬对 m6A 修饰的影响，以及 mA-自噬轴在肿瘤进展和治疗抵抗中的作用。此外，我们总结了 mA-自噬轴中关键分子在肿瘤诊断和治疗中的价值和应用前景。
