The crosstalk of m6A modification and non-coding RNAs in ferroptosis regulation in human diseases.

In recent years, N6-methyladenosine (m6A) modification has stood out as a key epitranscriptional mechanism. It governs nearly all stages of RNA metabolism-from RNA processing and nuclear export to translation and degradation. Non-coding RNAs (ncRNAs)-a broad category that includes microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and PIWI-interacting RNAs (piRNAs)-represent a major class of RNA transcripts with no ability to code for proteins. A bidirectional regulatory link exists between m6A modification and ncRNAs: m6A modification impacts the expression levels of ncRNAs, while ncRNAs can fine-tune the expression of proteins involved in m6A regulation. Ferroptosis is a unique form of non-apoptotic cell death driven by iron. It is defined by the accumulation of lipid peroxides and reactive oxygen species, and has been connected to a range of pathological conditions-such as metabolic diseases, neurological disorders, and malignant tumors. This review centers on the crosstalk between m6A modification and ncRNAs. It also summarizes the roles and underlying mechanisms of this interaction in controlling ferroptosis across multiple common diseases. What we aim for is to deepen understanding of this regulatory axis and provide valuable insights into potential therapeutic approaches for human diseases linked to ferroptosis.