Table 2 The role and regulatory mechanism of m6A regulator in cancer drug resistance
From: Biological and pharmacological roles of m6A modifications in cancer drug resistance
m6A regulator | Cancer type | Role in cancer | Expression in cancer drug resistance | Drug | Target genes | Mechanism | Ref |
|---|---|---|---|---|---|---|---|
METTL3 | BC | Oncogene | High | Adriamycin | MALAT1 | METTL3 promoted MALAT1 protein and activated MALAT1/E2F1/AGR2 axis | [127] |
METTL3 | NSCLC | Oncogene | NA | Cisplatin | YAP | METTL3 enhanced the translation of YAP mRNA by recruiting YTHDF1/3 and eIF3b | [128] |
METTL3 | HCC | Oncogene | Low | Sorafenib | FOXO3 | METTL3 promoted FOXO3 stability through a YTHDF1-dependent mechanism | [80] |
METTL3 | HCC | Oncogene | High | Adriamycin | ERRγ | METTL3 delayed the half-life of precursor mRNA of ERRγ | [45] |
METTL3 | CRC | Oncogene | NA | Oxaliplatin or irinotecan | CBX8 | METTL3 enhanced CBX8 mRNA stability through an IGF2BP1-dependent mechanism | [95] |
METTL3/14 | CRC | NA | NA | anti-PD-1 antibodies | STAT1 and IRF1 | METTL3 or METTL14 loss promoted IFN-c-Stat1-Irf1 signaling through stabilizing the Star1 and Irf1 mRNA via YTHDF2 | [101] |
METTL3,WTAP | NSCLC | Oncogene | NA | Crizotinib | c-MET | The downregulation of METTL3 and WTAP decreased c-MET expression | [91] |
WTAP | BLCA | Oncogene | High | Cisplatin | TNFAIP3 | Circ0008399 bound to WTAP and activated the circ0008399/WTAP/TNFAIP3 pathway | [129] |
WTAP | NKTCL | Oncogene | High | Cisplatin | DUSP6 | WTAP enhanced DUSP6 expression | [130] |
WTAP | BC | Oncogene | High | Adriamycin | DLGAP1-AS1 | WTAP motivated DLGAP1-AS1 stability | [131] |
FTO | GBM | Oncogene | NA | Temozolomide | PDK1 | JPX interacted with FTO and degraded PDK1 expression | [132] |
FTO | MM | Oncogene | High | Bortezomib | SOD2 | FTO downregulated the expression of SOD2 | [133] |
FTO | BC | Oncogene | High | Doxorubicin | STAT3 | FTO could activate STAT3 signaling in BC cells | [134] |
FTO | CSCC | Oncogene | High | Cisplatin | β-Catenin | FTO promoted gene expression of β-catenin via m6A modification | [135] |
FTO | Leukemia | Oncogene | High | Imatinib, nilotinib, or PKC412 | MERTK and BCL-2 | m6A demethylated by FTO promoted MERTK and BCL-2 stability | [69] |
ALKBH5 | PC | Tumor suppressor | Low | Gemcitabine | WIF-1 | ALKBH5 promoted WIF-1 transcription to hinder Wnt signaling | [87] |
ALKBH5 | EOC | Oncogene | High | Cisplatin | JAK2 | The ALKBH5-HOXA10 loop jointly activated the JAK2/STAT3 signaling pathway | [136] |
ALKBH5 | T-ALL | Oncogene | High | Glucocorticoid | USP1 | ALKBH5 increased USP1 and Aurora B expression | [137] |
ALKBH5 | EOC | Oncogene | Low | Olaparib | FZD10 | Downregulation of FTO and ALKBH5 contributed to FZD10 mRNA upregulation | [138] |
ALKBH5 | OSCC | Oncogene | High | Cisplatin | FOXM1 | ALKBH5 promoted FOXM1 expression by demethylating its nascent transcripts | [139] |
YTHDF1 | NSCLC | Oncogene | Low | Cisplatin | Keap1 | YTHDF1 promoted the translational efficiency of Keap1 | [140] |
IGF2BP3 | CRC | NA | High | Doxorubicin | ABCB1 | IGF2BP3 promoted the stability and expression of ABCB1 mRNA | [141] |
HNRNPC | GC | Oncogene | High | 5-FU, paclitaxel, or cisplatin | NA | mAb 5B2 targeted HNRNPC overexpressed in chemo-resistant GC cells | [30] |