Table 2.
RNA modification regulates lactate or lactylation
| Classification | Regulator (Type) | Modification | Target (Site) | Mechanism | Outcome | Refs. |
|---|---|---|---|---|---|---|
| Glycolytic Enzymes | ||||||
| HK | METTL3 (Writer), IGF2BP2/3 (Reader) | m6A | HK2 and GLUT1(5’/3’UTR) | Enhancing HK2 and GLUT1 mRNAs stability | Enhancing glycolysis, lactate production and tumor progression | [86, 91–93] |
| METTL3 (Writer), YTHDF1 (Reader) | m6A | HK2 (3’UTR) | Increasing HK2 mRNA stability | Promoting glycolysis, lactate production and CC cell proliferation | [78] | |
| KIAA1429 (Writer), HuR (Reader) | m6A | HK1 (CDS) | Jointly improving HK1 mRNA stability | Enhancing glycolysis and increasing sorafenib resistance in HCC | [94] | |
| RBM15 (Writer) | m6A | HK2 (3’ UTR) | Enhancing HK2, GPI, and PGK1 mRNAs stability | Promoting glycolysis and osteosarcoma progression | [95] | |
| IGF2BP2 (Reader), FTO and ALKBH5 (Eraser) | m6A | HK2 | Increasing HK2 mRNA stability | Enhancing glycolysis and promoting tumor progression | [86, 96, 97] | |
| PFK-1 | YTHDC1 (Reader) | m6A | PFKM (CDS) | Enhancing the stability and translation of PFKM and LDHA mRNAs | Enhancing glycolysis, lactate production and promoting OS progression | [98] |
| YTHDF2 (Reader), FTO (Eraser) | m6A | PFKP and LDHB | Enhancing PFKP and LDHB mRNAs stability | Enhancing glycolysis and promoting leukemia progression | [99] | |
| Aldolase | YTHDF2 (Reader), FTO (Eraser) | m6A | ALDOA (CDS) | Enhancing ALDOA mRNA stability | Enhancing glycolysis and promoting HCC growth under hypoxia | [79] |
| IGF2BP2 (Reader) | m6A | ALDOA | Enhancing ALDOA mRNA stability and translation | Enhancing glycolysis and histone lactylation, and promoting liver fibrosis | [89] | |
| Enolase | METTL3 (Writer), YTHDF1 (Reader), ALKBH5 (Eraser) | m6A | ENO1 (ORF 359 A) | Enhancing ENO1 mRNA translation | Promoting glycolysis, lactate production and LUAD tumorigenesis | [100] |
| KIAA1429 (Writer) | m6A | ENO1 (CDS 2273–2278) | Enhancing ENO1 mRNA stability | Promoting aerobic glycolysis and OC progression | [101] | |
| WTAP (Writer) | m6A | ENO1 (3’UTR) | Promoting ENO1 mRNA stability | Promoting breast cancer glycolysis | [102] | |
| METTL3 (Writer) | m6A | LINC00520 (183nt, 710nt) | Indirectly promoting ENO1 stability | Enhancing glycolysis, lactate production and inducing cisplatin resistance in OS | [103] | |
| PK | HNRNPC (Reader) | m6A | PKM (motif GGACU near exon 9) | Regulating PKM alternative splicing and promoting PKM2 expression | Promoting glycolysis, lactate production and progression in PTC | [104] |
| ALYREF (Reader) | m5C | PKM2 (3’UTR) | Enhancing PKM2 mRNA stability | Promoting glycolysis, lactate production and bladder cancer cell proliferation | [80] | |
| METTL1 (Writer) | m7G | PKM | Increasing PKM mRNA stability | Enhancing glycolysis and promoting immune evasion in CRC | [77] | |
| METTL14 (Writer), IGF2BP (Reader), ALKBH5 (Eraser) | m6A | JMJD8 (3’UTR) | Enhancing the enzymatic activity of PKM2 | Enhancing glycolysis, lactate production and promoting CRC progression | [105] | |
| PDK4 | IGF2BP3 (Reader), YTHDF1 (Reader) | m6A | PDK4 (5’UTR) | Enhancing PDK4 mRNA stability and translation | Enhancing glycolysis, lactate production | [106] |
| METTL16 (Writer), IGF2BP1 (Reader) | m6A | SOGA1 | Indirectly upregulating PDK4 expression | Promoting glycolysis and CRC progression | [107] | |
| LDH | IGF2BP3 (Reader) | m6A | LDHA (3’UTR) | Enhancing LDHA mRNA stability | Boosting lactate production and GC immune evasion | [108] |
| LRPPRC (Reader) | m6A | LDHA (3’UTR) | Enhancing LDHA mRNA stability | Enhancing glycolysis and TNBC progression | [82] | |
| METTL3 (Writer), YTHDF1 (Reader) | m6A | LDHA (CDS) | Promoting LDHA mRNA translation | Promoting glycolysis, tumor progression and 5-FU resistance | [81, 109, 110] | |
| NAT10 (Writer) | ac4C | JunB | Indirectly upregulating LDHA expression | Enhancing glycolysis and promoting TNBC progression and immunosuppression | [111] | |
| YTHDF2 (Reader) | m6A | Inc-Dpf3 (3812–3815 nt and 3852–3855 nt) | Indirectly upregulating LDHA expression | Promoting dendritic cell glycolysis metabolism and migration | [84] | |
| YTHDF3 (Reader) | m6A | lncRNA DICER1-AS1 (exon region) | Indirectly promoting LDHA, HK2 expression | Promoting glycolysis, lactate production and pancreatic cancer progression | [83] | |
| Transporters | ||||||
| GLUT1 | METTL3 (Writer) | m6A | GLUT1 (CDS/3 ‘UTR) | Enhancing GLUT1 mRNA translation | Enhancing glycolysis, lactate production and promoting tumor progression | [112, 113] |
| METTL3 (Writer) | m6A | GLUT1 | Enhancing GLUT1 mRNA stability | Promoting lactate production, progression and resistance to mTOR inhibitors in ccRCC | [114] | |
| WTAP (Writer), IGF2BP2 (Reader) | m6A | PIGT (3 ‘UTR) | Promoting GLUT1 glycosylation and membrane trafficking | Promoting glycolysis, proliferation and metastasis of bladder cancer cells | [115] | |
| YTHDF2 (Reader), FTO (Eraser) | m6A | GLUT1 and PKM2 | Enhancing GLUT1, PKM2 and c-Myc mRNAs stability | Promoting glycolysis and progression in HCC | [87] | |
| MCT | ALKBH5 (Eraser) | m6A | MCT4 | Enhancing the MCT4 mRNA stability | Promoting lactate production and the infiltration of Tregs and MDSCs in the TME | [88] |