Table 5.
Functions of m6A RNA modification in metabolic reprogramming of cancer
| m6A regulators | Molecules | Function | Reference |
|---|---|---|---|
| Glucose metabolism | |||
| METTL3 | HK2, GLUT1 | METTL3 interacts with the 3′ UTR regions of HK2 and GLUT1 mRNA and enhances its stability, thereby activating the glycolysis pathway | 119 |
| ALKBH5 | CK2α | ALKBH5 specifically recognizes the m6A sites of the 3′ UTR in CK2α mRNA and reduces its stability to inhibit cell glycolysis and proliferation | 121 |
| FTO | PKM2 | FTO triggers the m6A demethylation of PKM2 mRNA and accelerates its translation, thus promoting hepatocellular carcinoma tumorigenesis | 122 |
| YTHDF1 | Wnt signaling | YTHDF1 facilitates the translation of the Wnt signaling effectors TCF7L2 and TCF4, which are required for the maintenance of intestinal stem cells during regeneration and tumorigenesis | 86 |
| YTHDF2 | MEK/ERK | YTHDF2 weakens EGFR mRNA stability in an m6A-dependent manner and thus impairs the MEK/ERK pathway and consequently impedes cell proliferation and growth | 123 |
| METTL3 | NF-κB pathway | METTL3 enhances the translation of IKBKB and RELA and activates NF-κB pathway to promote bladder cancer progression | 124 |
| METTL14 | PI3K/Akt | METTL14 overexpression inactivates the PI3K/Akt pathway in high glucose-treated HK2 cells via PTEN-regulated HDAC5-mediated EMT of renal tubular cells in diabetic kidney disease | 125 |
| YTHDF2 | 6PGD | YTHDF2 binds directly to the m6A modification site in the 3′ UTR of the 6-phosphogluconate dehydrogenase (6PGD) gene to promote 6PGD mRNA translation in lung cancer cells | 126 |
| Lipid metabolism | |||
| METTL3 | miR-3619-5p/HDGF | METTL3 promotes the stability of lncRNA LINC00958 and activates the miR-3619-5p/HDGF axis to facilitate lipogenesis in HCC | 128 |
| FTO | SREBP1c/CIDEC | FTO increases lipid accumulation by activating the SREBP1c/CIDEC signaling pathway in an m6A-dependent manner in HepG2 cells | 129 |
| Glutamine metabolism | |||
| FTO, ALKBH5 | D2-HG | FTO and ALKBH5 are α-KG-dependent dioxygenases that are competitively inhibited by structurally related metabolite d-2-hydorxyglutarate (D2-HG), leading to abnormal expression of isocitrate dehydrogenase 1 or 2 (IDH1/2)-mutant tumors | 130,131 |
| YTHDF1 | GLS1 | YTHDF1 accelerates GLS1 translation, a key enzyme of glutamine metabolism, and promotes colon cancer development | 132 |