m6A modification in non-coding RNAs: Mechanisms and potential therapeutic implications in fibrosis

Abstract

N6-methyladenosine (m⁶A) is one of the most prevalent and reversible forms of RNA methylation, with increasing evidence indicating its critical role in numerous physiological and pathological processes. m⁶A catalyzes messenger RNA(mRNA) as well as regulatory non-coding RNAs (ncRNAs), such as microRNAs, long non-coding RNAs, and circular RNAs. This modification modulates ncRNA fate and cell functions in various bioprocesses, including ncRNA splicing, maturity, export, and stability. Key m⁶A regulators, including writers, erasers, and readers, have been reported to modify the ncRNAs involved in fibrogenesis. NcRNAs affect fibrosis progression by targeting m⁶A regulators. The interactions between m⁶A and ncRNAs can influence multiple cellular life activities. In this review, we discuss the impact of the interaction between m⁶A modifications and ncRNAs on the pathological mechanisms of fibrosis, revealing the possibility of these interactions as diagnostic markers and therapeutic targets in fibrosis.