Autophagy: a critical mechanism of N6-methyladenosine modification involved in tumor progression and therapy resistance.

Abstract

N⁶-Methyladenosine (m⁶A) is an evolutionarily highly conserved epigenetic modification that affects eukaryotic RNAs, especially mRNAs, and m⁶A 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 m⁶A 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 m⁶A, which in turn affects the levels of their target genes via m⁶A modification. Thus, m⁶A 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 m⁶A modification on autophagy as well as the effects of autophagy on m⁶A modification and the roles of the m⁶A-autophagy axis in tumor progression and therapy resistance. Additionally, we summarized the value and application prospects of key molecules in the m⁶A-autophagy axis in tumor diagnosis and therapy.