Ferroptosis: a critical mechanism of N6-methyladenosine modification involved in carcinogenesis and tumor progression

Ferroptosis is an iron-dependent regulatory cell necrosis induced by iron overload and lipid peroxidation. It occurs when multiple redox-active enzymes are ectopically expressed or show abnormal function. Hence, the precise regulation of ferroptosis-related molecules is mediated across multiple levels, including transcriptional, posttranscriptional, translational, and epigenetic levels. N-6-methyladenosine (m(6)A) is a highly evolutionarily conserved epigenetic modification in mammals. The m(6)A modification is commonly linked to tumor proliferation, progression, and therapy resistance because it is involved in RNA metabolic processes. Intriguingly, accumulating evidence suggests that dysregulated ferroptosis caused by the m(6)A modification drives tumor development. In this review, we summarized the roles of m(6)A regulators in ferroptosis-mediated malignant tumor progression and outlined the m(6)A regulatory mechanism involved in ferroptosis pathways. We also analyzed the potential value and application strategies of targeting m(6)A/ferroptosis pathway in the clinical diagnosis and therapy of tumors.