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Table 2 Oncogenic signaling pathways modulated by m6A modification regulators

From: The m6A RNA methylation regulates oncogenic signaling pathways driving cell malignant transformation and carcinogenesis

Signaling pathway Cancer type m6A regulator(s) Up/downstream target(s) Functional outcome/correlation Reference
Wnt/β-catenin Hepatoblastoma (HB) ↑ METTL3 ↓ miR-186 (upstream of METTL3) Increased proliferation, vascular invasion, metastasis, tumor recurrence [29]
Hepatoblastoma (HB) ↑ METTL3 ↑ CTNNB1 Increased tumor growth [30]
Epithelial ovarian carcinoma (EOC) ↓ FTO
↓ ALKBH5
↑ IGF2BP2
↑ FZD10 Resistance to PARP inhibitors (PARPi) [31]
Osteosarcoma (OS) ↑ METTL3 ↑ Lymphoid enhancer-binding factor 1 (LEF1) Increased tumorigenesis [32]
Pancreatic cancer (PC) ↓ ALKBH5 ↓Wnt inhibitory factor 1 (WIF-1) Increased cancer cell proliferation, migration, and invasion
Enhanced chemoresistance
[33]
Colorectal cancer (CRC) ↑ YTHDF1 ↑ FZD9 and WNT6 Enhanced tumorigenicity and cancer stem cell formation [34]
Gastric cancer (GC) ↑ YTHDF1 ↑ FZD7 Aggressive gastric tumor development [35]
Gastric cancer (GC) ↓ METTL3
↓ METTL14
↑ FTO
↑ β-Catenin
↑ Axin
Increased proliferation and invasiveness [36]
PI3K/Akt/mTOR Endometrial cancer ↓ METTL3
↓ METTL14 (R298P Mut)
↓ PHLPP2
↑ PRR5, PRR5L and mTOR
Increase proliferation and tumorigenicity [37]
Endometrial cancer ↑ FTO Unspecified Increased proliferation and invasiveness [38]
Gastric cancer (GC) ↓ METTL14
↑ FTO
Unspecified Increased proliferation and invasiveness [36]
Ovarian cancer ↑ METTL3 ↑ miR-126-5p Increased ovarian cancer cell proliferation, migration and invasion
Decreasing apoptosis
[39]
GI Cancers (Colorectal, gastric, esophageal, pancreatic, liver) ↓ METTL14
↑ FTO
↑ PTEN, Akt1, PIK3CA and mTOR Poor overall patient survival [40]
Nasopharyngeal carcinoma (NPC) ↑ YTHDC2 ↑ Insulin-like growth factor 1 receptor (IGF1R) Increased radiation resistance [41]
Renal cell carcinoma (RCC) ↓ METTL3 Unspecified Cancer progression, decreased overall survival [42]
Cervical cancer ↑ hnRNPA2B1 Unspecified Increased proliferation, migration and invasiveness [43]
Breast cancer ↑ FTO Unspecified Increased metabolic activity [44]
High-grade serous ovarian carcinoma (HGSOC) ↑ WTAP Unspecified Increased cell proliferation and migration
Decreased apoptosis
Poor overall patient survival
[45]
Pancreatic cancer (PC) ↑ YTHDF2 ↑ GSK3β Increased cell proliferation [46]
JAK-STAT Hepatocellular carcinoma (HCC) ↑ METTL3
↑ YTHDF2
↓ SOCS2 Increased HCC progression, poor overall and disease-free survival [47]
Colorectal cancer (CRC) ↑ METTL3 ↓ SOCS2
↑ LGR5
Increased stemness and chemoresistance [48]
Gastric cancer (GC) ↑ METTL3 ↓ SOCS2 Increased cancer cell proliferation [49]
MAPK  
ERK1/2 Renal cell carcinoma (RCC) ↓ METTL14
↑ FTO
↓ RBM15B
↑ P2RX6 Increased RCC migration and invasion [50]
p38/ERK Colorectal cancer (CRC) ↓ METTL3 Unspecified Increased tumor size, tumor advancement and metastasis [51]
Raf/MEK/ERK Colorectal cancer (CRC) ↑ METTL3 Pri-miR-1246
(↑ miR-1246)
Increased invasiveness and metastasis [52]
Ras/Raf/ERK Hepatocellular carcinoma (HCC) ↑ METTL3 ↓ RDM1 Increased tumor progression [53]
  Gastric cancer (GC) ↑ METTL3 ↓ BATF2 Increased gastric carcinogenesis [54]
p38 MAPK Colorectal cancer (CRC) ↓ YTHDC2 Unspecified Decreased apoptosis [55]
  High-grade serous ovarian carcinoma (HGSOC) ↑ WTAP Unspecified Increased cell proliferation and migration
Decreased apoptosis
Poor overall patient survival
[45]
  Hepatocellular carcinoma (HCC) ↓ YTHDF2 ↓ EGFR Increased HCC cell proliferation [56]
p53 pathway Pancreatic cancer (PC) ↓ ALKBH5 ↓ PER1 Increased cell proliferation and invasiveness [57]
Clear cell renal cell carcinoma (ccRCC) ↑ METTL3
↑ METTL14
Unspecified Poor disease prognosis and overall survival [58]
Esophageal carcinoma (ESCA) ↑ HNRNPC Unspecified Activation of cell cycle progression [59]
Colorectal cancer (CRC) ↑ METTL3 ↑ mut-p53 mRNA Increased chemoresistance [60]
Non-small cell lung cancer (NSCLC) ↑ FTO ↑ USP7 Increased cancer cell proliferation [61]
Hepatocellular carcinoma (HCC) ↑ METTL3 ↓ RDM1 Increased tumor progression [53]
Hippo pathway Non-small cell lung cancer (NSCLC) ↑ METTL3
↑ YTHDF1
↑ YTHDF3
↑ YAP1
↑ MALAT1 (lncRNA)
Increased invasiveness and chemoresistance [62]
Non-small cell lung cancer (NSCLC) ↑ ALKBH5 ↓ YAP1 Decreased tumor growth, invasiveness, metastasis and EMT [63]
Lung adenocarcinoma (LUAD) ↑ METTL3 ↑ TAZ Increased cell growth, survival and invasiveness [64]
Colorectal cancer (CRC) ↓ METTL14 Pri-miR-375
(↓ miR-375)
Tumor progression
Poor overall patient survival
[65]
Pancreatic cancer (PC) ↑ YTHDF2 ↑ Mob1 Suppressed migration, invasiveness and EMT [46]
NFκB pathway Malignant transformed hepatocyte stem-like cells ↑ METTL3 CUDR (upstream)
SUV39H1 (downstream)
Malignant transformation of hepatocyte stem-like cells [66]
MCF7/ADR
HepG2/ADR
↑ METTL3 ↑ ERRγ Chemoresistance [67]
Ovarian cancer ↑ ALKBH5 ↑ NANOG Carcinogenesis, increased cancer stem cells [68]
Bladder cancer (BCa) ↑ METTL3 ↑ MYC Increased cancer cell proliferation, migration and decreased apoptosis [69]
Hedgehog pathway Prostate cancer ↑ METTL3 ↑ GLI1 Increased cancer cell survival, proliferation and invasiveness [70]
Notch pathway Glioma ↑ METTL3 ↑ DLL1, DLL3, JAG2, NOTCH1–3 and HES1 Increased tumorigenesis [71]
Snail pathway Liver cancer ↑ METTL3
↑ YTHDF1
↑ Snail Increased tumor progression [72]
Hepatocellular carcinoma (HCC) ↑ METTL3 ↑ SUMO1 (upstream)
↑ Snail (downstream)
HCC progression [73]