Table 2.
RNA modifying regulators of m6A in Urologic cancers
| Cancer type | Category | m6A regulations | expression | property | Biological functions | Mechanism | Signaling pathways | Related genes | Refs. |
|---|---|---|---|---|---|---|---|---|---|
| PCa | Writer | METTL3 | Up | Oncogene | Proliferation, invasion, and migration | Inhibition expression of LHPP mRNA and NEX3-1 mRNA | AKT | YTHDF2, LHPP, NEX3-1 | [167] |
| Writer | METTL3 | Up | Oncogene | Proliferation | Enhance expression of GLI1 mRNA | c-Myc/Cyclin D1 | SHH, GLI1 | [160] | |
| Writer | METTL3 | Up | Oncogene | Proliferation | Enhance expression of LEF1 mRNA | Wnt/β-catenin | LEF1 | [168] | |
| Writer | METTL3 | Up | Oncogene | Proliferation, invasion, and migration | Enhance expression of ARHGDIA mRNA | EMT | ARHGDIA | [169] | |
| Writer | METTL3 | Up | Oncogene | Proliferation | Promote the maturation of pri-miR-182 | Wnt/β-catenin | DGCR8, miR-182 | [170] | |
| Writer | METTL3 | Up | Oncogene | Invasion and migration | Enhance KIF6C mRNA stability | IGF2BP3/KIF3C | KIF3C, KIF6C, IGF2BP3 | [171] | |
| Writer | METTL3 | Up | Oncogene | Proliferation | Enhance expression of MALAT mRNA | PI3K/AKT | MALAT | [172] | |
|
Writer Writer Writer |
METTL3 METTL3 METTL3 |
Up Up Up |
Oncogene Oncogene Oncogene |
Proliferation Bone metastasis Glycolysis |
Enhance expression of PVT1 mRNA Enhance expression of PCAT6 mRNA Enhance SNHG7 mRNA stability |
miR-27b-3b/BLM PCAT6/IGF2BP2/IGF1R c-Myc |
PVT1 IGF2BP2, IGF1R SNHG7, SRSF1 |
[173] [174] [178] |
|
| Writer | METTL14 | Up | Oncogene | Proliferation, invasion, and angiogenesis | Inhibition expression of THBS6 mRNA | / | THBS6 | [180] | |
|
Eraser Eraser |
FTO FTO |
Down Down |
Suppression Suppression |
Proliferation Proliferation, invasion, and migration |
Inhibition expression of MC4R Reduced degradation of CLIC4 mRNA |
/ / |
MC4R CLIC4 |
[183] [184] |
|
| Reader | YTHDF1 | Up | Oncogene | Proliferation, invasion, and migration | Enhance expression of PLK1 | PI3K/AKT | ELK1, PLK1 | [188] | |
| Reader | YTHDF1 | Up | Oncogene | Proliferation, invasion, and migration | Enhance expression of TRIM44 | / | TRIM44 | [189] | |
| Reader | YTHDF2 | UP | Oncogene | Proliferation, invasion, and migration | Induction of MOB3b mRNA degradation | KDM5a/miRNA-495/YTHDF2/ m6A-MOB3b | KDM5a, miR-495, MOB3b | [190] | |
| Reader | IGF2BP2 | Up | Oncogene | Proliferation, bone metastasis | Enhance expression of PCAT6 mRNA, Enhance IGF1R stability | PCAT6/IGF2BP2/IGF1R | PCAT6, IGF1R | [174] | |
| Reader | IGF2BP3 | Up | Oncogene | Invasion and migration | Binding of circular RNA hsa_circ_0003258 enhances the stability of HDAC4 mRNA, activates the ERK pathway, and triggers EMT | ERK, EMT | HDAC4, hsa_circ_0003258 | [194] | |
| BCa | Writer | METTL3 | Up | Oncogene | Invasion and migration | Enhance expression of AFF4 mRNA | NF-κb, Myc | AFF4 | [196] |
| Writer | METTL3 | Up | Oncogene | Proliferation and immune escape | c-JUN binds to the METTL3 promoter, increases the expression of METTL3 and global m6A levels, and suppresses PD-L1 expression abundance | JUN | c-JUN | [197] | |
|
Writer/ Reader |
METTL3/YTHDF2 | Up | Oncogene | Invasion and migration | Degradation of mRNA of tumor suppressors SETD7 and KLF4 | METTL3/YTHDF2 m6A | SETD7, KLF4 | [198] | |
| Writer | METTL3 | Up | Oncogene | Cell adhesion | YTHDF1/3/ITGA6 | ITGA6 | [199] | ||
| Writer | METTL3 | Up | Oncogene | Proliferation and angiogenesis | Enhance expression of TEK and VEGF-A mRNA | / | TEK, VEGF-A | [200] | |
| Writer | METTL3 | Up | Oncogene | Promotes malignant transformation of urinary tract epithelial cells | mediates effective site-specific m6A mounting on CDCP1 mRNA | / | CDCP1 | [201] | |
| Writer | METTL3 | Up | Oncogene | Proliferation, invasion, migration, and angiogenesis | PM2.5 Induced METTL3 promoter hypermethylation and increased binding affinity of transcription factor HIF1A to enhance METTL3 expression | HIF1A/METTL3/IGF2BP3/BIRC5/VEGFA | HIF1A, BIRC5,VEGFA | [203] | |
| Writer | METTL14 | Up | Oncogene | Proliferation | Enhancing the stability of Notch1 mRNA | Notch | Notch1 | [204] | |
| Eraser | FTO | Up | Oncogene | Proliferation and invasion | Regulation of CDK6 expression | FTO/miR-576/CDK6 | MiR-576, CDK6 | [206] | |
| Eraser | FTO | Up | Oncogene | Proliferation and invasion | Regulation of demethylase activity on PYCR1 | / | USP18, PYCR1 | [207] | |
|
Eraser Reader |
FTO YTHDF1 |
Up Up |
Oncogene Oncogene |
Proliferation, invasion, and migration Proliferation |
Regulation of MALAT1 expression / |
MALAT/miR-384/MAL2 YTHDF1-RPN2-PI3K/AKT/mTOR |
MALAT1, miR-384, MAL2 METTL3, PRN2 |
[208] [210] |
|
| Reader | IGF2BP3 | Up | Oncogene | Cell cycle and proliferation | / | JAK/STAT | / | [212] | |
| RCC | Writer | METTL3 | Up | Oncogene | Tumor migration and stem cell-like tumorigenic cells | Enhance expression of ABCD1 mRNA | / | ABCD1 | [214] |
| Writer | METTL14 | Down | Suppression | Proliferation, invasion, and migration | Regulation expression of BPTF mRNA | BPTF/ENO2/SRC | BPTF, ENO2, SRC | [215] | |
| Writer | METTL14 | Down | Suppression | Proliferation, invasion, and migration | Regulation expression of P2X6 mRNA | P2X6-Ca2+-p-ERK1/ERK2-MMP9 | P2X6, MMP9 | [216] | |
| Writer | METTL3/14 | Down | Suppression | Invasion and migration | Enhance expression of MUC15 and HRG mRNA | / | MCU15, HRG | [217] | |
| Writer | WTAP | Up | Oncogene | Proliferation, invasion, and migration | Enhancement of S1PR3 mRNA stability and performance in an IGF2BPs-dependent manner | PI3K/AKT | SIRP3, miR-501-3p, CDK2 | [217–219] | |
|
Writer Eraser |
RBM15 FTO |
Up Up |
Oncogene Oncogene |
Proliferation Inhibits autophagy and promotes proliferation |
Enhance expression and stability of CXCL11 Regulation expression of SIK2 mRNA |
EP300/CBP/RBM15/CXCL11 / |
EP300, CBP, CXCL11 SIK2, IGF2BP2 |
[221] [224] |
|
| Eraser | ALKBH5 | Up | Oncogene | Proliferation, invasion, and migration | Regulation expression of AURKB mRNA | / | AURKB | [222] | |
| Eraser | ALKBH5 | Down | Suppression | Proliferation, invasion, and migration | Regulation expression of PLOD2 mRNA | / | PLOD2 | [223] | |
| Reader | IGFBP1 | Down | Suppression | Energy metabolism | Regulation expression of LDHA mRNA | / | LDHA | [231] | |
| Reader | IGFBP3 | Down | Suppression | Proliferation | Enhance activity of CDK4, COL6A1, LAMA5 and FN1 | / | CDK4, COL6A1, LAMA5, FN1 | [232] | |
| TC | Writer | METTL3 | Up | Oncogene | Drug-resistance | Enhance expression and stability of TFAP2C mRNA | / | TFAP2C | [236] |