Table 3 The role and mechanism of m6A regulators in EC
m6A regulators | Roles | Genes/RNAs | Mechanisms | Model | Refs. |
|---|---|---|---|---|---|
Writers | |||||
METTL3/METTL14 | Tumor suppressor | PHLPP2; mTORC2 | METTL14 mutation or reduced METTL3 reduces the level of m6A methylation, leading to decrease expression of the negative AKT regulator PHLPP2 and increase expression of the positive AKT regulator mTORC2 | In vitro; in vivo | [168] |
WTAP | Oncogene | CAV-1 | WTAP methylates 3′‐UTR of CAV‐1 and downregulates CAV‐1 expression to activate NF‐κB signaling pathway | In vitro; in vivo | [159] |
Readers | |||||
YTHDF2 | Oncogene | FENDRR | YTHDF2-mediated LncRNA FENDRR degradation promotes cell proliferation by elevating SOX4 expression | In vitro; in vivo | [170] |
YTHDF2 | Tumor suppressor | IRS1 | YTHDF2 binds the methylation sites of target transcripts IRS1 and promotes IRS1 mRNA degradation, consequently inhibiting the expression of IRS1 and inhibiting IRS1/AKT signaling pathway | In vitro | [169] |
IGF2BP1 | Oncogene | PEG10 | IGF2BP1 can recognize m6A sites in the 3′UTR of PEG10 mRNA and recruit PABPC1 to enhance PEG10 mRNA stability, which consequently promotes PEG10 protein expression | In vitro; in vivo | [176] |
IGF2BP1 | Oncogene | SOX2 | Dysregulation of IGF2BP1 by PADI2/MEK1/ERK signaling results in abnormal accumulation of oncogenic SOX2 expression | In vitro; in vivo | [183] |
Erasers | |||||
FTO | Oncogene | HOXB13 | FTO demethylates m6A modifications in HOXB13 mRNA and promotes EC metastasis by activating the WNT signaling pathway | In vitro; in vivo | [146] |
ALKBH5 | Oncogene | IGF1R | ALKBH5 demethylates target transcripts IGF1R and enhances IGF1R mRNA stability, consequently promoting IGF1R translation and activating IGF1R signaling pathway | In vitro | [189] |
ALKBH5 | Oncogene | SOX2 | ALKBH5 in promoting SOX2 transcription via mRNA demethylation, thereby maintaining the stem-like state and tumorigenicity potential of ECSCs | In vitro; in vivo | [197] |
Immunoregulators | |||||
ZCH3H13, METTL14, and YTHDC1 | NA | NA | the expression, mutation, and SCNAs of these genes are associated with the immune cell infiltration | NA | [198] |