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Table 1 Oncogenic roles of m6A proteins and biological mechanisms exerted in human tumors

From: Mechanism of RNA modification N6-methyladenosine in human cancer

Cancer Regulator Role in cancer Mechanism Functional classification Refs
AML METTL3 Oncogene Promote translation of MYC, BCL2 and PTEN Inhibit differentiation of HSPCs, increase cancer cells growth and inhibit apoptosis [41]
AML METTL14 Oncogene Stabilize MYC and MYB Inhibit differentiation and promote leukemia cells self-renewal [42]
AML WTAP Oncogene Target rapamycin (mTOR) expression and PMA Promote AML cells proliferation and block the differentiation [43]
AML FTO Oncogene Destabilize ASB2 and RARA Promote leukemic oncogene-mediated cells transformation and leukemogenesis [44]
[45]
Stabilize MYC and CEBPA Increase proliferation/survival of cancer cells
AML YTHDF2 Oncogene Stabilize mRNAs like Tal1 Inhibit HSCs expansion [46]
AML IGF2BP1 Oncogene Form LIN28B/let-7/IGF2BP1 signaling axis Increase leukemia cells growth and metabolism [47]
GBM METTL3 Oncogene Upregulate SOX2 Attenuate differentiation, enhance DNA repair and tumor growth [48]
GBM FTO Oncogene Upregulate oncogenes like ADAM19/EPHA3/KLF4 Promote GSCs growth and self-renewal [49]
GBM ALKBH5 Oncogene Promote tumorigenesis by stabilizing FOXM1 mRNA Sustain tumor cells proliferation program [50]
LC METTL3 Oncogene Enhance translation of EGFR and TAZ Promote growth, survival, and invasion of cancer cells [51]
[52]
[53]
[54]
[55]
Targeted by miR-33a Promote the proliferation of NSCLC cells
Enhance translation of BRD4 via eIF3 Promotes tumorigenicity
Promote YAP translation by regulating miR-1914-3p Induce invasion and metastasis of NSCLC
Regulate miR-143-3p/VASH1 axis Induce brain metastasis and angiogenesis
LC FTO Oncogene Enhance MZF1 expression and stabilize MZF1 transcript Facilitate cancer cells proliferation and invasion [56]
[57]
Strengthen the stability of USP7 mRNA Promote cancer cells growth
LC YTHDF2 Oncogene Facilitate METTL3-mediated SOCS2 m6A modification Induce LC cells growth and metastasis [58]
LC IGF2BP1 Oncogene Increase SRF stability Promote tumor cells growth and enhance cells invasion [59]
NPC METTL3 Oncogene Stress the ZNF750-FGF14 signaling axis Promote NPC growth and inhibit cells apoptosis [60]
HCC METTL3 Oncogene Promote SOCS2 degradation Induce HCC cells proliferation, migration, and colony formation [58]
[61]
Regulate EMT key translator Snail Activate the migration, invasion and EMT of cancer cells
HCC KIAA1429 Oncogene Inhibit ID2 mRNA Facilitate the migration and invasion of cancer cells [62]
[63]
Induce HuR separation and degrade GATA3 pre-mRNA Induce the tumor growth and metastasis
HCC WTAP Oncogene Silence of ETS1 via m6A-HuR-dependent mechanism Promote the proliferation capability and tumor growth of HCC cells [64]
HCC YTHDF2 Oncogene Downregulate miR-145
Facilitate METTL3-mediated SOCS2 m6A modification
Promote proliferation of HCC cells
Induce HCC cells proliferation, migration, and colony formation
[65]
[58]
HCC IGF2BP1 Oncogene Increase SRF mRNA stability Promote tumor cells growth and enhance cells invasion [59]
HB METTL3 Oncogene Stabilize CTNNB1 via Wnt/β-catenin pathway Promote the proliferation of HB [66]
CRC METTL3 Oncogene Upregulate lncRNA RP11 Facilitate the migration, invasion and EMT of CRC cells [67]
[68]
[69]
[70]
Maintain SOX2 expression via IGF2BP2 Sustain CRC cells self-renewal, stem cell frequency and migration
Regulate miR-1246/SPRED2/ MAPK signaling Promote the metastasis and migration of CRC cells
Upregulate CBX8 assisted by IGF2BP1 Maintain the stemness properties of cancer cells
CRC FTO Oncogene Downregulate miR-1266 Promote the proliferation of CRC cells [71]
[72]
Initiate cellular signaling molecules like STAT3 NM
CRC WTAP Oncogene Form WTAP-WT1-TBL1 axis Inhibit cell apoptosis and cell cycle arrest and promote cell proliferation [73]
CRC YTHDC2 Oncogene Upregulate HIF-1α Activate cell metastasis [74]
CRC YTHDF1 Oncogene Promoted by c-Myc Promote the proliferation of CRC cells [75]
[76]
Inhibit Wnt/β-catenin pathway activity Promote the cell cycle progression and the tumorigenicity of CRC cells
CRC IGF2BP1 Oncogene Bind CBX8 mRNA and promote CBX8 expression Maintain the stemness properties of cancer cells [70]
[77]
[31]
IGF2BP2 Oncogene Stabilized by lncRNA LINRIS Promote tumor growth and the aerobic glycolysis in CRC
IGF2BPs Oncogene Promote MYC Promote cell proliferation, colony formation ability, migration and invasion
PDAC METTL3 Oncogene Promote miR-25-3p maturation and activation of AKT-p70S6K Promote cell proliferation, migration, and invasion [78]
PDAC YTHDF2 Oncogene Activate AKT pathway Promote cell proliferation [79]
GC METTL3 Oncogene Enhance HDGF mRNA Promote proliferation, liver metastasis, tumor angiogenesis and glycolysis in GC [80]
GC ALKBH5 Oncogene Decrease methylation of lncRNA NEAT1 Promote invasion and metastasis of GC [81]
BCA METTL3 Oncogene Accelerate pri-miR221/222 maturation Sustain tumor proliferation of BCA [82]
[83]
[84]
Form AFF4/NF-κB/MYC signaling axis Promote BCA cell proliferation, invasion, tumorigenicity and survival
Promote CDCP1 translation Promote malignant transformation of uroepithelial cells and BCA tumorigenesis
PCA YTHDF2 Oncogene Target miR-493-3p Promote PCA cells proliferation and migration [85]
PCA METTL3 Oncogene Regulate hedgehog pathway Facilitate cell proliferation, survival, colony formation, and invasion [86]
RCC WTAP Oncogene Enhance CDK2 expression Enhance cell proliferation abilities [87]
CSCC FTO Oncogene Target β-catenin Promote chemo-radiotherapy resistance of CSCC in vitro and in vivo [88]
[89]
Promote transcripts of E2F1 and MYC Facilitate cell proliferation and migration
BC METTL3 Oncogene Form a positive feedback loop of METTL3/HBXIP/let-7 g Promote cell proliferation and inhibit cell apoptosis [90]
    Target BCL-2 Accelerate the proliferation, inhibit the apoptosis and the tumor growth [91]
BC ALKBH5 Oncogene Stabilize NANOG and KLF4 Increase the percentage of BCSCs and phenocopy the effect of hypoxia [92]
   Oncogene Target TGFβ1 signaling–associated transcripts Promote cell growth, invasion, inappropriate cell cycle activity and evasion of apoptosis [93]
BC FTO Oncogene Target BNIP3 Promote BC cells proliferation, colony formation and metastasis [94]
EOC METTL3 Oncogene Upregulate AXL translation Increase cellular proliferation, motility, invasion, and tumor formation and promote EMT [95]
EOC ALKBH5 Oncogene Target miR-7 and BCL-2 Promote the proliferation and invasion in vitro and in vivo via inhibiting the autophagy [96]
EOC IGF2BP1 Oncogene Sustain the expression of SRF-target oncogenes Promote tumor cells growth and enhance cell invasion [59]
Melanoma FTO Oncogene Target PD-1, CXCR4, SOX10, CTSV2, and NOP16 Increase tumor growth and decrease response to anti-PD-1 blockade immunotherapy [97]
cSCC METTL3 Oncogene Promote Np63 expression Promote cSCC cell stem-like properties like colony forming ability and tumorigenicity [98]
EBV METTL14 Oncogene EBNA3C hijacks METTL14 Induce proliferation and colony formation of EBV positive cells [99]
  1. AML acute myeloid leukemia; GBM glioblastoma; LC lung cancer; NPC nasopharyngeal carcinoma; HCC hepatocellular carcinoma; HB hepatoblastoma; CRC colorectal cancer; PDAC pancreatic cancer; GC gastric carcinoma; BCA bladder cancer; PCA prostate cancer; RCC renal cell carcinoma; CSCC cervical squamous cell carcinom; BC breast cancer; EOC epithelial ovarian cancer; cSCC cutaneous squamous cell carcinoma; EBV EBV-associated cancer; NM not mentioned