RNA m6A methylation regulates the malignancy and apoptosis of colorectal cancer cells via modulation of P53 expression

Abstract N6-Methyladenosine (m6A) modification, which is methylated by methyltransferase-like 3 (METTL3), is critical for the progression of several cancers. However, the roles of m6A in the apoptosis of cancer cells have not been well illustrated. Our present study reveals that deletion of METTL3 promotes the apoptosis and impairs the migration and invasion of colorectal cancer (CRC) cells. Both sequencing analysis and in vitro assays confirm that P53, an important transcription factor of apoptosis, is involved in the m6A-regulated apoptosis of CRC. Mechanically, the occurrence of m6A in P53 coding region (CDS), but not 3’ untranslated region (UTR), inhibited the expression of P53. Loss and gain functional studies confirm that YTHDF2 mediates mRNA degradation of P53 mRNA in an m6A-dependent manner. Moreover, METTL3 up-regulation acts as an adverse prognosis factor for recurrence‐free survival of colorectal cancers. Our study highlights the critical roles of m6A in the regulation of apoptosis, in cancer cells, through modulation of P53 expression.