RNA N6 -methyladenosine (
m6A) modification occurs in approximately 25% of mRNAs at the transcriptome-wide level.
RNA m6A is regulated by the
RNA m6A methyltransferases methyltransferase-like 3 (METTL3), METTL14, and METTL16 (writers), demethylases FTO and ALKBH5 (erasers), and
binding proteins YTHDC1-2, YTHDF1-3, IGF2BP1-3, and SND1 (readers). These RNA m6A modification
proteins are frequently upregulated or downregulated in human
cancer tissues and are often associated with poor patient prognosis. By modulating
pre-mRNA splicing,
mRNA nuclear export, decay, stability, and translation of oncogenic and
tumor suppressive transcripts, RNA m6A modification
proteins regulate
cancer cell proliferation, survival, migration, invasion,
tumor initiation, progression,
metastasis, and sensitivity to anticancer
therapies. Importantly, small-molecule activators of METTL3, as well as inhibitors of METTL3, FTO, ALKBH5, and IGF2BP1 have recently been identified and have shown considerable anticancer effects when administered alone or in combination with other
anticancer agents, both in vitro and in mouse models of human
cancers. Future compound screening and design of more potent and selective RNA m6A modification
protein inhibitors and activators are expected to provide novel
anticancer agents, appropriate for clinical trials in patients with
cancer tissues harboring aberrant RNA m6A modification
protein expression or RNA m6A modification
protein-induced resistance to
cancer therapy.