Table 1 The roles of m6A regulators in normal hematopoiesis and leukemogenesis
From: Functions of RNA N6-methyladenosine modification in acute myeloid leukemia
Type | m6A regulators | Role in cancer | Target genes | Biological functions | Mechanism | Upstream | Reader | Refs |
|---|---|---|---|---|---|---|---|---|
Leukemogenesis | METTL3 | Oncogene | MYC, BCL2, PTEN | Promotes cell proliferation and colony formation, as well as inhibits differentiation and apotosis | Promotes translation of MYC, BCL2, PTEN and inhibits pAKT pathway | No study | No study | [67] |
METTL3 | Oncogene | SP1 | Promotes cell proliferation and inhibits differentiation | Promotes translation of SP1 | CEBPZ | No study | [68] | |
METTL14 | Oncogene | MYB, MYC | Promotes cell proliferation, as well as inhibits differentiation and apotosis | Enhances mRNA stability and promotes translation of MYB and MYC | SPI1 | No study | [69] | |
WTAP | Oncogene | MYC | Promotes cell proliferation, colony formation and chemoresistance, as well as inhibits differentiation | Suppresses MYC mRNA stability | No study | No study | [70] | |
WTAP | Oncogene | No study | Promotes cell proliferation, colony formation and chemoresistance, as well as inhibits differentiation | The molecular chaperone Hsp90 maintains the protein stability of WTAP | No study | No study | [71] | |
FTO | Oncogene | MYC, CEBPA | Promotes cell proliferation | Enhances mRNA stability of MYC and CEBPA | No study | YTHDF2 | [53] | |
FTO | Oncogene | ASB2, RARA | Promotes cell proliferation and colony formation, as well as inhibits differentiation and apotosis | Suppresses mRNA stability of ASB2 and RARA | No study | No study | [72] | |
FTO | Oncogene | PFKP, LDHB | Promotes aerobic glycolysis | Enhances mRNA stability of PFKP and LDHB | No study | YTHDF2 | [73] | |
FTO | Oncogene | MERTK, BCL2 | Promotes cell proliferation and drug resistance | Enhances mRNA stability of MERTK and BCL2 | No study | YTHDF2 | [74] | |
FTO | Oncogene | LILRB4 | Promotes decitabine-induced immune evasion and makes AML cells more resistant to T cell cytotoxicity | Enhances LILRB4 mRNA stability | No study | YTHDF2 | [75] | |
ALKBH5 | Oncogene | AXL | Promotes cell proliferation and colony formation, as well as inhibits differentiation and apotosis | Enhances AXL mRNA stability | KDM4C, MYB, Pol II | YTHDF2 | [76] | |
ALKBH5 | Oncogene | TACC3 | Promotes cell proliferation and colony formation, as well as inhibits apoptosis | Enhances TACC3 mRNA stability | No study | No study | [77] | |
YTHDF2 | Oncogene | TNFR2 | Promotes cell proliferation and inhibits apotosis | Suppresses TNFR2 mRNA stability | No study | / | [78] | |
IGF2BP1 | Oncogene | ALDH1A1, HOXB4, MYB | Promotes cell proliferation, colony formation and chemoresistance, as well as inhibits differentiation | Enhances expression of ALDH1A1, HOXB4, and MYB through posttranscriptional regulation | No study | / | [79] | |
Normal hematopoiesis | METTL3 | / | notch1a | Promotes HSPCs generation through the endothelial-to-haematopoietic transition (EHT) | Suppresses notch1a mRNA stability and inhibits Notch signaling pathway | No study | YTHDF2 | [80] |
METTL3 | / | No study | Maintains HSCs in a quiescent state | No study | No study | No study | [81] | |
YTHDF2 | / | Wnt target genes | Maintains HSCs in a quiescent state | Facilitates mRNAs decay of Wnt target genes and represses Wnt signaling | No study | / | [82] | |
YTHDF2 | / | Tal1 | Maintains HSCs in a quiescent state | Facilitates mRNAs degradation of multiple key transcription factors (e.g., Tal1) | No study | / | [83] | |
YTHDF2 | / | Inflammation related genes | Sustains HSC integrity and reconstitutes multilineage hematopoiesis upon aging | Facilitates mRNAs degradation of inflammation related genes | No study | / | [84] |