Skip to main content

Table 2 m6A methylation in cancer metabolic reprogramming

From: Advances in the role of m6A RNA modification in cancer metabolic reprogramming

Metabolism Molecules Underlying mechanism in metabolism References
Glucose metabolism HK2, GLUT1 m6A modification was closely correlated with glycolysis pathway activation in colorectal cancer patients’ tissues. Mechanically, HK2, and GLUT1 were found to be regulated by m6A modification and participate in glycolysis activation in colorectal cancer [17]
  PKM2 FTO triggered the m6A demethylation of PKM2 mRNA and accelerated the translated production, thus promoting hepatocellular carcinoma tumorigenesis [96]
  PIK3CB A missense variant rs142933486 in PIK3CB reduced the PIK3CB m6A level and facilitated its mRNA and protein expression levels mediated by the m6A “writers” complex (METTL3/METTL14/WTAP) and YTHDF2 [97]
  EGFR, MEK/ERK signaling YTHDF2 negatively modulated the EGFR mRNA stability in HCC via its binding the m6A site in the EGFR 3′-UTR, which in turn impaired the MEK/ERK pathway and consequently impedes the cell proliferation and growth [102]
  NF-κB signaling METTL3 positively regulated MYD88 expression through controlling m6A methylation status of MYD88-RNA, leading to the activation of NF-κB signaling [103]
  NF-κB signaling METTL3 activated NF-κB signaling by promoting the expression of IKBKB and RELA through regulating translational efficiency [94]
  AKT signaling m6A methylation normally attenuates AKT activity in the endometrium by promoting the m6Adependent translation of PHLPP2 and m6A-dependent degradation of transcripts encoding subunits of mTORC2, increasing proliferation and tumorigenicity in endometrial cancer [14]
  AKT signaling The association between m6A and AKT signaling was also confirmed in multiple tumor types including leukemia cells and clear cell renal cell carcinoma [101, 117]
Lipid metabolism ACC1, ACLY, DGAT2, EHHADH, FASN, FOXO, PGC1A, and SIRT1 ACC1, ACLY, DGAT2, EHHADH, FASN, FOXO, PGC1A, and SIRT1 were dramatically decreased in livers of hepatocyte-specific METTL3 knockout mice. CD36 and LDLR were also downregulated by improving the expression of FASN through its m6A demethylase activity [106]
  SREBP1c, CIDEC FTO increased lipid accumulation by a novel FTO/SREBP1c/CIDEC signaling pathway in an m6A-dependent manner in HepG2 cells [108]
  SREBP1c, FASN, SCD1, ACC1 YTHDF2 could also bind to the mRNA of SREBP1c, FASN, SCD1, and ACC1, to decrease their mRNA stability and inhibit gene expression [109]
  AMPK m6A modification resulted in reduced AMPK activity [110]
  FAM225A m6A was highly enriched within FAM225A and enhanced its RNA stability [111]
Glutamine metabolism α-KG FTO and ALKBH5 are α-KG-dependent dioxygenases and competitively inhibited by the structurally related metabolite D2-HG [114, 115]