Table 1.
Roles of m6A regulators in different cancers
Cancer | m6A regulator | Role in cancer | Mechanism | References |
---|---|---|---|---|
AML | METTL3 | Oncogene | Promotes AML progression by promoting the translation of c‐MYC, BCL‐2 and PTEN mRNAs | 57 |
METTL3 | Oncogene | Be recruited by CEBPZ to promoters of a specific set of active gene (SP1) and increased translation, resulting in the maintenance of a leukaemic state | 58 | |
METTL14 | Oncogene | Enhances MYB and MYC expression, promotes myeloid differentiation of HSPCs and AML cells and leukaemogenesis | 56 | |
WTAP | Oncogene | Induces abnormal proliferation and arrested differentiation of leukaemia cells | 24 | |
FTO | Oncogene | Promotes leukaemic oncogene‐mediated cell transformation and leukemogenesis and weakens the therapeutic effect of ATRA | 62 | |
FTO | Oncogene | Be inhibited by R‐2HG, resulting in anti‐tumour effect via targeting FTO/m6A/MYC/CEBPA signalling | 63 | |
Glioblastoma | METTL3, METTL14 | Tumour suppressor | Inhibits GSC self‐renewal and tumorigenesis by down‐regulating oncogenes (ADAM19, EPHA3 and KLF4) and up‐regulating tumour suppressor genes (CDKN2A, BRCA2 and TP53I11) | 68 |
WTAP | Oncogene | Be correlated with glioma grade and poor postoperative survival in glioma patients | 71 | |
ALKBH5 | Oncogene | Maintains tumorigenicity of GSC by sustaining FOXM1 expression and cell proliferation programme | 72 | |
BC | METTL3 | Oncogene | Promotes cell proliferation via HBXIP/let‐7g/METTL3/HBXIP positive feedback loop | 74 |
KIAA1429 | Oncogene | Promotes BC progression by regulating CDK1 by an m6A‐independent manner | 75 | |
ALKBH5 | Oncogene | Promotes NANOG mRNA and protein expression and mediates enrichment of BCSCs in the hypoxic tumour microenvironment | 76 | |
FTO | Oncogene | Promoted cell proliferation, colony formation and metastasis by abrogating the m6A modification of BNIP3 mRNA and epigenetically down‐regulating BNIP3 | 78 | |
HCC | METTL3 | Oncogene | Promoted cell proliferation, colony formation and metastasis by abrogating the m6A modification of BNIP3 mRNA and epigenetically down‐regulating BNIP3 | 79 |
METTL14 | Tumour suppressor | Be inversely correlated with OS and RFS of HCC patients and inhibits tumour metastasis in vitro and in vivo by modulating the pri‐miRNA 126 process in an m6A‐dependent manner via interacting with DGCR8 | 81 | |
FTO | Oncogene | Be correlated with poor prognosis of HCC individuals and promotes tumorigenesis by mediating demethylation of PKM2 mRNA | 83 | |
Hepatoblastoma | METTL3 | Oncogene | Serves as a diagnostic and prognostic biomarker and promotes tumour growth in vivo by regulating CTNNB1 expression via m6A modification and activating Wnt/β‐catenin signalling | 80 |
GC | METTL3 | Oncogene | P300‐mediated H3K27 acetylation promotes METTL3 expression, which mediates m6A modification on HDGF mRNA and enhances its stability by an IGF2BP3‐dependent manner, resulting in tumour angiogenesis, GC growth and liver metastasis | 89 |
FTO | Oncogene | Be an increased expression in 375 GC from TCGA data set | 92 | |
CRC | METTL3 | Tumour suppressor | Acts as an independent prognostic factor and suppresses cell proliferation and migration through p38/ERK pathways | 94 |
METTL3 | Oncogene | Mediates m6A modification of CBX8 mRNA and promotes its expression, which maintains the stemness and inhibits the chemosensitivity of CRC | 95 | |
METTL3 | Oncogene | Promotes lncRNA RP11 expression by an m6A‐dependent manner, which targets Siah1/Fbxo45/Zeb1 axis to drive cell dissemination and development of CRC | 96 | |
FTO | Oncogene | Low expression of microRNA‐1266 promotes CRC progression via targeting FTO | 97 | |
YTHDC2 | Oncogene | Be correlated with CRC progression and promotes the cell metastatic ability via promoting translation of HIF‐1α | 99 | |
Lung cancer | METTL3 | Oncogene | miR‐33a or miR‐600 suppresses cell proliferation, migration and invasion by targeting METTL3 | 101, 102 |
ALKBH5 | Oncogene | Promotes cell proliferation and invasion by decreasing m6A level on FOXM1 mRNA and increasing its translation under intermittent hypoxia | 106 | |
FTO | Oncogene | Promotes cell proliferation by increasing the stability of USP7 mRNA | 104 | |
FTO | Oncogene | Promotes progression of lung squamous cell carcinoma by reversing m6A modification of MZF1 mRNA and increasing its stability | 105 | |
Bladder cancer | METTL3 | Oncogene | Be correlated with poor prognosis of bladder cancer patients and promotes cell proliferation in vitro and in vivo and tumorigenesis by modulating the pri‐miR221/222 process in an m6A‐dependent manner via interacting DGCR8 | 108 |
METTL3 | Oncogene | Promotes bladder cancer progression via AFF4/NF‐kappaB/MYC signalling network | 109 | |
RCC | METTL14 | Tumour suppressor | m6A (METTL14) suppressed P2RX6 activation promotes cell migration and invasion through ATP‐induced Ca2 + influx modulating ERK1/2 phosphorylation and MMP9 signalling pathway | 111 |
WTAP | Oncogene | Be related to poor prognosis of RCC patients and stabilizes CDK2 transcript to enhance CDK2 expression to promote cell proliferation and tumorigenesis in vivo | 112 | |
Pancreatic cancer | METTL3 | Oncogene | Be correlated with poor prognosis of patients with pancreatic cancer and promotes cell proliferation, invasion, migration and chemo‐ and radioresistance | 114, 115 |
WTAP | Oncogene | Be associated with poor overall survival for pancreatic ductal adenocarcinoma | 116 | |
ALKBH5 | Tumour suppressor | Inhibits pancreatic cancer motility by decreasing lncRNA KCNK15‐AS1 methylation | 118 | |
FTO | Oncogene | Promotes cell proliferation by enhancing stability of c‐Myc mRNA | 117 | |
YTHDF2 | Unknown | Promotes cell proliferation possibly via Akt/GSK3β/Cyclin D1 pathway and inhibits cell migration and invasion probably via up‐regulation of total YAP | 119 | |
Cervical cancer | FTO | Oncogene | Contributes to the chemoradiotherapy resistance of cervical squamous cell carcinoma through up‐regulation β‐catenin via mRNA demethylation and the subsequent activation of ERCC1 | 122 |
FTO | Oncogene | Be correlated with cervical cancer progression and promotes cell proliferation and migration via controlling m6A modification of E2F1 and Myc transcripts | 123 | |
Endometrial cancer | METTL3, METTL14 | Tumour suppressor | Inhibits cell proliferation, anchorage‐independent growth, and migration and in vivo tumour growth through activation of the AKT pathway | 120 |
Ovarian epithelial cancer | ALKBH5 | Oncogene | Be related to poor OS and progression‐free survival, promotes cell proliferation and invasion, and inhibits autophagy through the interaction between Bcl‐2 and Beclin‐1 and the EGFR‐PI3K‐AKT‐mTOR pathway | 124 |
Cutaneous cancer | METTL3 | Oncogene | Promotes colony formation and invasion of melanoma cells by regulating MMP2 | 125 |
METTL3 | Oncogene | Promotes cSCC cell colony‐forming ability in vitro and tumorigenicity in vivo through modulating ΔNp63 in an m6A‐dependent manner | 126 | |
Nasopharyngeal carcinoma | METTL3 | Oncogene | Mediates m6A modification of ZNF750 mRNA and blocks its expression, which promotes cell growth through regulating FGF14 | 127 |
Osteosarcoma | METTL3 | Oncogene | Promotes cell progression by regulating the m6A level of LEF1 and activating Wnt/β‐catenin signalling pathway | 128 |
Cholangiocarcinoma | WTAP | Oncogene | Increases cell motility and tumorigenicity in vivo | 129 |