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. N⁶-methyladenosine (m⁶A) is a highly evolutionarily conserved epigenetic modification in mammals. The m⁶A 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 m⁶A modification drives tumor development. In this review, we summarized the roles of m⁶A regulators in ferroptosis-mediated malignant tumor progression and outlined the m⁶A regulatory mechanism involved in ferroptosis pathways. We also analyzed the potential value and application strategies of targeting m⁶A/ferroptosis pathway in the clinical diagnosis and therapy of tumors.