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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 â–³Np63 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