Fig. 8.

Mechanism of m⁶A on cancer cell metabolism. m⁶A modulates metabolism via various mechanisms in cancers. (A) METTL3‐modified m⁶A on 5′UTR of PDK4 is recognized by YTHDF1/eEF‐2 and IGF2BP3 to promote the glycolysis and ATP generation in both cervical and liver cancer cells [25]. (B) METTL3 targets GLUT1 to increase its mRNA, which actives mTORC1 pathway to promote glucose uptake and lactate production in CRC cells [250]. (C) WTAP targets 3′UTR of HK2 to enhance its stability, which is recognized by YTHDF1 to promote glycolytic capacity in GC cells [251]. (D) FTO downregulation promotes the YTHDF1‐medicated translation of MYC, which increases glycolysis in LC cells [252]. (E) YTHDF1 recognizes both 5′UTR an 3′ UTR m⁶A of TFRC, promoting its translation to enhance iron metabolism in hypopharyngeal squamous cell carcinoma [53]. (F) YTHDF2 binds to 6PGD mRNA to facilitate its translation, which enhances the activity of the PPP flux in LC cells [253]. (G) METTL3 increases HDGF‐involved lipogenesis by upregulating lncRNA LINC00958 in HCC cells [134]. (H) METTL3 targets lncRNA SNHG7 to increase its mRNA level. SNHG7 regulated c‐Myc via interacting with SRSF1 to promote glycolysis via SRSF1/c‐Myc axis in PRAD cells [254]. (I) YTHDC1 promotes the maturation of miR‐30d to increase its expression, which further regulates the expression of RUNX1, SLC2A1 and HK1 and therefore attenuates the Warburg effect in pancreatic ductal adenocarcinoma cells [62]. (J) circRHBDD1 recruits YTHDF1 to the m⁶A‐modifed PIK3R1 mRNA and accelerates its translation to augment aerobic glycolysis via activation of PI3K/AKT signaling in HCC [247].