N6-Methyladenosine: an RNA modification as a central regulator of cancer.
Review
Overview
abstract
N6-Methyladenosine (m6A) is a modified nucleotide in mRNAs and non-coding RNAs that influences gene expression, primarily by promoting the degradation of specific transcripts. Recent studies have highlighted the dynamic and context-dependent roles of this RNA modification in cancer, implicating it in tumorigenesis, immune evasion and therapeutic resistance. In this Review, we discuss the functional roles of m6A writers, erasers and readers in cancer. We highlight how m6A dysregulation contributes to oncogenic processes, including cell differentiation and immune microenvironment remodelling. Using haematological malignancies as an example, we highlight the principles of m6A-dependent regulation that may be broadly relevant across cancer types. Notably, inhibitors targeting the m6A writer methyltransferase-like 3 (METTL3) have emerged as potential cancer therapeutics. METTL3 inhibitors not only disrupt m6A-dependent pathways but also elevate double-stranded RNA levels, activating innate immune responses and antitumour immunity. We emphasize the need for high-resolution quantitative m6A mapping in cancer and mechanistic studies to better understand the specific transcripts that exhibit altered patterns of m6A in cancer and to identify patient subgroups most likely to benefit from METTL3 inhibitors.
