Table 2.
m6A modulations in cancer therapeutic resistance.
| Cancers | m6A-enymases | Drug resistance | Mechanisms | References |
|---|---|---|---|---|
| NSCLC | METTL3 | Increase resistance to DDP | MALAT1-miR-1914-3p-YAP axis via recruiting YTHDF1/3 and eIF3b | [93] |
| Lung cancer | m6A modulation | Increase resistance to afatinib | m6A-modified genes increase | [94] |
| Melanoma | FTO | Increase resistance to IFNγ and anti-PD-1 treatment | Inhibit m6A methylation of protumorigenic melanoma cell-intrinsic genes including PD-1 (PDCD1), CXCR4, and SOX10 | [99] |
| Leukemia | FTO | Increase resistance to TKIs | Regulate mRNA stability of proliferation/survival transcripts bearing m6A and protein synthesis | [100] |
| CSCC | FTO | Increase chemo-radiotherapy resistance | Decrease m6A methylation of β-catenin and then increase ERCC1 activity | [101] |
| PDAC | ALKBH5 | Decrease resistance to gemcitabine | Change its target genes via Global m6A profile | [102] |
| BRCA-mutated EOC cells | FTO and ALKBH5 | m6A modification of FZD10 mRNA increase resistance to PARPi | Wnt/β-catenin pathway induces m6A modification of FZD10 mRNA via downregulation of FTO and ALKBH5 | [19] |
| Colon cancer | m6A methylation | CBX8 increases chemoresistance | m6A methylation promotes CBX8 mRNA stability to increase CBX8 | [103] |
| OSCC | ALKBH5 | DDX3 increase resistance to cisplatin | DDX3 modulates ALKBH5 to reduce m6A methylation in FOXM1 and NANOG nascent transcript and increases CSC population | [104] |
NSCLC: non-small cell lung cancer; CSCC: Cervical squamous cell carcinoma; PDAC: pancreatic ductal adenocarcinoma; EOC: epithelial ovarian cancers; OSCC: Oral squamous cell carcinoma.