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Table 1 The roles of m6A-associated proteins in digestive system tumours

From: Function and clinical significance of N6-methyladenosine in digestive system tumours

Tumour type m6A Regulators Role in M6A Mechanism Function in cancer Reference
ESCC FTO Eraser Targets MMP13 Promotes tumour progression [32]
  METTL3 Reader Activates Wnt3/β-catenin and AKT signaling pathway Promotes tumour proliferation and invasion [33]
  ALKBH5 Eraser Inhibits tumour progression [36]
  HNRNPC Reader Promotes tumour progression [36]
  HNRNPA2B1 Reader Up-regulates fatty acid synthase ACLY and ACC1 Promotes tumour proliferation, metastasis and invasion [35]
  YTHDC2 Reader [37]
GC METTL3 Writer Promotes the m6A modification of GFI1 Promotes tumour cell proliferation and migration [44]
    METTL3/HDGF/GLUT4/ENO2 pathway Promotes tumour progression [46]
    METTL3/ZMYM1/E-cadherin pathway Promotes tumour progression [45]
    METTL3/BATF2/p53/ERK pathway Promotes tumour proliferation and metastasis [48]
    Promotes the m6A modification of MYC Promotes tumour progression [51]
    Regulates several components of
MYC gene (such as MCM5, MCM6, etc.)
[50]
  METTL14 Writer PI3K/AKT/mTOR pathway Inhibits tumour proliferation and invasion [53]
  YTHDF1 Reader YTHDF1/FZD7/β-catenin pathway Promotes tumour progression [54]
  WTAP Writer Promotes tumour progression [60]
  FTO Eraser Promotes tumour proliferation, metastasis and invasion [55]
  ALKBH5 Eraser Decreases methylation of the lncRNA NEAT1 Promotes tumour metastasis and invasion [143]
CRC METTL3 Writer METTL3/IGF2BP2/SOX2 pathway Promotes tumour progression [63]
    Stabilizes CCNE1 mRNA Promotes tumour progression [64]
    METTL3/miR-1246/SPRED2 /MAPK pathway Promotes tumour progression [65]
    Suppresses SOCS2 expression Promotes tumour progression [66]
    METTL3/HK2/GLUT1/IGF2BPs pathway Promotes tumour progression [67]
    METTL3/GLUT1/mTORC1 pathway Promotes tumour progression [144]
    P38 / ERK pathway Inhibits tumour progression [62]
    The expression of p53 missense mutation Acquired multidrug resistance [69]
  METTL14 Writer Inhibits the expression of SOX4 Inhibits tumour progression [70]
    METTL14/miR-375/YAP1 pathway Inhibits tumour metastasis [71]
    METTL14/miR-375/SP1 pathway Inhibits tumour metastasis and invasion [71]
    METTL14/YTHDF2/lncRNA pathway Inhibits tumour progression [72]
  YTHDF1 Reader Up-regulates the expression of FZD9 and WNT6 and activate Wnt/β-catenin pathway Promotes tumour progression [81]
  IGF2BP2 Reader RNA-protein ternary complex Promotes tumour progression [79]
  IGF2BP1 Reader Upregulates the stability and expression of c-Myc mRNA Promotes tumour progression [78]
  FTO Eraser Removes the m6A modification of MYC and enhance MYC expression Promotes tumour proliferation, metastasis and invasion [76]
HCC WTAP Writer HuR/ETS1/p21/p27 pathway Promotes tumour progression [88]
  KIAA1429 Writer Inhibits ID2 expression Promotes tumour metastasis and invasion [89]
    Degrade GATA3 pre-mRNA Promotes tumour proliferation and metastasis [90]
    KIAA1429/circ-KIAA1429/ZEB1 pathway Promotes tumour proliferation, metastasis and invasion [91]
  YTHDF1 Reader PI3K/AKT/mTOR pathway Promotes tumour proliferation [93]
  YTHDF3 Reader M6A/YTHDF3/ZEB1 pathway Promotes tumour proliferation, metastasis and invasion [91]
  YTHDF2 Reader Degrades IL11 and SERPINE2
mRNA
Inhibits tumour proliferation [94]
    Degrades EGFR mRNA Inhibits tumour progression [95]
    Promotes tumour metastasis [96]
  METTL14 Writer Up-regulates miR-126 expression Inhibits tumour metastasis [97]
  METTL3 Writer UBC9/SUMOylated METTL3/Snail pathway Promotes tumour progression [106]
    METTL3/miR-873-5p/SMG1 pathway Promotes tumour progression [107]
    METTL3/IGF2BP2/FEN1 pathway Promotes tumour progression [102]
    METTL3/HBXIP/HIF-1α pathway Promotes tumour progression [105]
    METTL3/YTHDF2/SOCS2 pathway Promotes tumour progression [100]
    Upregulated LINC00958 Promoted HCC lipogenesis and progression [112]
  ZCCHC4 Writer Promotes tumour proliferation [103]
  ALKBH5 Eraser ALKBH5 / LYPD1 pathway Inhibits tumour proliferation and invasion [104]
  FTO Eraser Inhibits tumour progression [111]
PDAC METTL3 Writer Promotes tumour proliferation and invasion [122]
    METTL3/miR-25-3p/PHLPP2-AKT pathway Promotes tumour progression [124]
  METTL14 Writer Decreases PERP mRNA expression Promotes tumour proliferation and migration [123]
  YTHDF2 Reader Promotes tumour proliferation [125]
  ALKBH5 Eraser Post-transcriptionally activates PER1 Inhibits tumour proliferation, metastasis and invasion [126]
    Demethylates lncRNA KCNK15-AS1 Inhibits tumour metastasis [127]
    Down-regulates the m6A level of WIF-1 and inhibit the activation of Wnt pathway Inhibits tumour progression [128]
  FTO Eraser Stabilizes bHLH mRNA Promotes tumour proliferation [129]
  IGF2BP2 Reader Up-regulates lncRNA DANCR expression Promotes tumour proliferation [130]
  1. ESCC esophageal squamous cell cancer, GC gastric cancer, CRC colorectal cancer, HCC hepatocellular carcinoma, PDAC pancreatic ductal adenocarcinoma