Table 2 The role and mechanism of m6A regulators in CC
m6A regulators | Roles | Genes/RNAs | Mechanisms | Model | Refs. |
|---|---|---|---|---|---|
Writers | |||||
METTL3 | Oncogene | miR-193b | METTL3 downregulates miR-193b to promote CC aggressiveness by targeting CCND1 | In vitro; in vivo | [99] |
METTL3 | Oncogene | ACIN1 | METTL3 interacts with IGF2BP3 to promote the mRNA stability of ACIN1 | In vitro; in vivo | [100] |
METTL3 | Oncogene | β-catenin | METTL3 indirectly suppresses CTNNB1 transcription via stabilizing its transcription suppressor E2F1 mRNA; METTL3 represses membrane localization of β-catenin and its interaction with E-Cadherin by downregulating c-Met kinase | In vitro; in vivo | [101] |
METTL3 | Oncogene | circ0000069 | circ0000069 is upregulated partially due to m6A modification, which promotes cell proliferation and migration via sponging miR-4426 in CC | In vitro; in vivo | [107] |
METTL3 | Oncogene | FOXD2-AS1 | METTL3/FOXD2-AS1 promotes the tumorigenesis of cervical cancer through the LSD1/p21 axis | In vitro; in vivo | [110] |
METTL3 | Oncogene | ZFAS1 | ZAFS1 sequesters miR-647, and this RNA–RNA interaction is regulated by METLL3-mediated m6A modification | In vitro; in vivo | [111] |
METTL3 | Oncogene | HK2 | METTL3 recruits YTHDF1 to enhance HK2 stability, there by promoting the Warburg effect of CC | In vitro; in vivo | [118] |
METTL14 | Oncogene | CYP1B1 | piRNA-14633 promotes proliferation, migration and invasion of CC cells by METTL14/CYP1B1 signaling axis | In vitro; in vivo | [106] |
Readers | |||||
YTHDF1 | Oncogene | RANBP2 | YTHDF1 regulates RANBP2 translation in an m6A-dependent manner without effect on its mRNA expression | In vitro; in vivo | [120] |
IGF2BP2 | Oncogene | MYC | E6/E7 promote CC by regulating MYC methylation sites via activating IGF2BP2 | In vitro; in vivo | [133] |
Readers | |||||
IGF2BP2 | Oncogene | circARHGAP12 | CircARHGAP12 interacts with IGF2BP2 to combine with FOXM1 mRNA, thereby accelerating the stability of FOXM1 mRNA | In vitro; in vivo | [127] |
YTHDF1/ IGF2BP3 | Oncogene | PDK4 | The m6A modified 5′UTR of PDK4 positively regulates its translation elongation and mRNA stability via binding with YTHDF1/eEF-2 complex and IGF2BP3, respectively | In vitro; in vivo | [116] |
IGF2BP3 | Oncogene | ACIN1 | METTL3 interacts with IGF2BP3 to promote the mRNA stability of ACIN1 | In vitro; in vivo | [100] |
IGF2BP3 | Oncogene | KCNMB2-AS1 | KCNMB2-AS1 and IGF2BP3 form a positive regulatory circuit that enlarge the tumorigenic effect of KCNMB2-AS1 in CC | In vitro; in vivo | [125] |
Erasers | |||||
FTO | Oncogene | E2F1; MYC | FTO regulates CC cells proliferation and migration via controlling m6A modification of E2F1 and MYC transcripts | In vitro | [137] |
FTO | Oncogene | β-catenin | FTO enhances the chemo-radiotherapy resistance through regulating expression of β-catenin by reducing m6A levels in its mRNA transcripts and in turn increases ERCC1 activity | In vitro; in vivo | [136] |
FTO | Oncogene | HOXC13-AS | FTO-stabilized HOXC13-AS epigenetically up-regulates FZD6 and activates Wnt/β-catenin signaling | In vitro; in vivo | [135] |
Immunoregulators | |||||
METTL3 | NA | NA | METTL3 expression is positively related to the density of CD33+ MDSCs in the TME | In-vitro | [150] |