Fig. 2
From: Biological and pharmacological roles of m6A modifications in cancer drug resistance
Dual effects of m6A in autophagy. On the one hand, the m6A modification inhibits autophagy. In hepatocellular carcinoma (HCC), METTL3 enhanced forkhead box O3 (FOXO3) mRNA stability and inhibited light chain 3-II (LC3-II) accumulation through a YTHDF1-dependent mechanism. The overexpression of FTO induced YTHDF2-dependent inhibition of unc-51-like kinase 1 (ULK1) mRNA decay and promoted LC3-II accumulation and autophagy. With the help of YTHDF2, FTO also increased the translation of autophagy-associated gene-5 (ATG5) and ATG7 mRNAs and promoted autophagosome assembly. On the other hand, m6A modification also promotes autophagy. In epithelial ovarian cancer (EOC), ALKBH5 slowed autophagy by cementing B-cell lymphoma 2 (BCL-2) mRNA stability and activating the EGFR-PIK3CA-AKT-mTOR pathway. Additionally, the m6A reader YTHDF3 promoted autophagy through the upregulation of FOXO3 mRNA translation