Background
Regulators of m6A
Type | Regulator | Function | Reference |
---|---|---|---|
m6A writer | METTL3 | catalyzes m6A modification | |
METTL14 | helps METTL3 to recognize the subtract | ||
METTL16 | catalyzes m6A modification | [15] | |
RBM15 | binds the m6A complex and recruit it to special RNA site | ||
VIRMA | recruits the m6A complex to the special RNA site and interacts with polyadenylation cleavage factors CPSF5 and CPSF6 | [18] | |
WTAP | contributes to the localization of METTL3-METTL14 heterodimer to the nuclear speckle | [19] | |
ZC3H13 | bridges WTAP to the mRNA-binding factor Nito | [20] | |
m6A eraser | ALKBH5 | removes m6A modification | [21] |
FTO | removes m6A modification | [22] | |
m6A reader | EIF3 | enhances mRNA translation | [23] |
HNRNPA2B1 | mediates mRNA splicing and primary microRNA processing | [24] | |
HNRNPC | mediates mRNA splicing | [25] | |
IGF2BPs | enhances mRNA stability and storage | [26] | |
YTHDC1 | contributes to RNA splicing and export | ||
YTHDC2 | enhances the translation of target RNA and reduces the abundance of target RNA | [29] | |
YTHDF1 | enhances mRNA translation | [30] | |
YTHDF2 | promotes mRNA degradation | ||
YTHDF3 | enhances translation and degradation by interacting with YTHDF1 and YTHDF2 |
Writers
METTL3
METTL14
METTL16
Erasers
FTO
Readers
YTHDF1
YTHDF2
YTHDF3
YTHDC1
YTHDC2
IGF2BPs
EIF3
Roles of m6A in cancer
cancer type | enzyme | target RNA | effect of enzyme on target RNA | role of m6A in cancer | reference |
---|---|---|---|---|---|
AML | METTL3 | c-MYC, BCL2, PTEN | translation | inhibits cell differentiation and apoptosis, promotes leukemia progression | [118] |
METTL3 | SP1 | translation | promotes cell proliferation and inhibits cell differentiation | [119] | |
Breast cancer | ALKBH5 | NANOG | stabilization | inhibits tumor formation and breast cancer stem cell population | [120] |
FTO | BNIP3 | degradation | inhibits breast cancer cell proliferation, colony formation and metastasis | [121] | |
METTL3 | HBXIP | expression | enhances proliferation, invasion and metastisis and inhibits apoptosis | [122] | |
CSCC | FTO | β-catenin | expression | enhances the chemo-radiotherapy resistance | [123] |
GSC | ALKBH5 | FOXM1 | expression | impairs proliferation and tumorigenicity | [21] |
METTL3 | SOX2 | stability | enhances of neurosphere formation | [124] | |
HCC | METTL14 | miRNA 126 | splicing | inhibits the migration and invasiveness of HepG2 cells and restrains tumor metastasis | [125] |
LUSC | FTO | MZF1 | stability | inhibits proliferation and invasion and increases apoptosis | [22] |
Ovarian cancer | METTL3 | AXL | translation | promotes growth and invasion of ovarian tumors | [126] |
Pancreatic cancer | ALKBH5 | KCNK15-AS1 | expression | promotes migration and invasion | [127] |
Renal cell carcinoma | FTO | PGC-1α | stability | enhances cell growth and facilitates apoptosis | [128] |
m6A functions as a tumor promoter
m6A promotes expression of oncogenes
m6A inhibits expression of tumor suppressor genes
m6A functions as a tumor suppressor
m6A inhibits expression of oncogenes
m6A promotes expression of tumor suppressor genes
The dual role of m6A in cancer
m6A affects cancer progression by modulating target gene
Factors affecting m6A modification and m6A enzymes in cancer
Therapeutic strategy based on m6A
tumor types | target RNA | function of target RNA | aberrant expression of m6A enzymes | readers | function of readers | change of target RNA level | reference |
---|---|---|---|---|---|---|---|
AML | MYC, MYB | oncogenic | METTL14↑ | EIF3 | translation | ↑ | [58] |
Bladder cancer | CDCP1 | oncogenic | METTL3↑ | YTHDF1 | translation | ↑ | [109] |
Colorectal carcinoma | SOX2 | oncogenic | METTL3↑, IGF2BP2↑ | IGF2BP2 | stabilization | ↑ | [80] |
Endometrial cancer | mTORC2 | oncogenic | METTL3↓ | YTHDF2 | degradation | ↑ | [110] |
PHLPP2 | antitumor | METTL3↓ | YTHDF1 | translation | ↓ | [110] | |
Gastric cancer | HDGF | oncogenic | METTL3↑ | IGF2BP3 | stabilization | ↑ | [111] |
HCC | EGFR | oncogenic | YTHDF2↓ | YTHDF2 | degradation | ↑ | [112] |
SOCS2 | antitumor | METTL3↑ | YTHDF2 | degradation | ↓ | [113] | |
Leukemia | MERTK,BCL-2 | oncogenic | FTO↑ | YTHDF2 | degradation | ↑ | [114] |
Liver cancer | Snail | oncogenic | METTL3↑ | YTHDF1 | translation | ↑ | [115] |
Lung cancer | BRD4, EGFR,TAZ | oncogenic | METTL3↑ | EIF3 | translation | ↑ | |
Ovarian cancer | SRF | oncogenic | IGF2BP1↑ | IGF2BP1 | stabilization | ↑ |