Types of tumor biological behavior | m6A regulators | Tumor types | Mechanism | Effects on biological behavior of tumors | References |
---|---|---|---|---|---|
Genomic instability | ALKBH5 | Lung cancer | ALKBH5 improves the translation efficiency of FOXM1 mRNA by downregulating m6A methylation in FOXM1 mRNA | Promotes proliferation and invasion of lung adenocarcinoma cells under hypoxia | [316] |
Genomic instability | METTL3 | Lung cancer | METTL3-catalyzed m6A methylation mediates HMBOX1 gene downregulation, resulting in telomere dysfunction and inactivation of the p53 signaling pathway | Promotes cancer cell proliferation | [257] |
Genomic instability | WTAP | HCC | WTAP downregulation suppresses the m6A methylation level, thereby blocking the G2/M phase transition | Mediates HCC occurrence | [317] |
Cell cycle | ALKBH5 | Renal cell carcinoma | Hypoxia-induced HIF-1α upregulates ALKBH5 expression | High ALKBH5 expression promotes tumor proliferation by increasing the percentage of cells in the G2/M phase | [250] |
Cell cycle | METTL3 | Uveal melanoma | Overexpression of METTL3 promotes tumor proliferation and colony formation by regulating the G1 phase | Promotes tumor proliferation | [309] |
Cell cycle | IGF2BP1 | HCC | The lncRNA HCG11 regulates IGF2BP1 to affect the G1 phase of HCC through MAPK signaling | Promotes tumorigenesis | [245] |
Cell cycle | IGF2BP1 | Renal cell carcinoma | IGF2BP1 promotes G1/S cell cycle transition by stabilizing mRNA | Enhances cell cycle progression and promotes tumor proliferation through m6A modifications | [318] |
Cell cycle | IGF2BP1 | Lung cancer | IGF2BP1 silencing induces cell cycle arrest and apoptosis through downregulation of Netrin-1 | Inhibits tumor progression | [244] |
Cell cycle | IGF2BP3 | Renal cell carcinoma | DMDRMR binds IGF2BP3 to stabilize target genes and enhances cell cycle kinase CDK4 and G1-S phase transition | Promotes tumor progression | [247] |
Autophagy | FTO | Kidney cancer | FTO-mediated demethylation prevents the decay of YTHDF2-dependent Unc-51-like kinase 1 mRNA by removing the methyl group from the 3′-UTR region | Promotes tumorigenesis | [226] |
Autophagy | ALKBH5 | Lung cancer | ALKBH5 improves the translation efficiency of lung cancer cells by decreasing the m6A methylation level of ubiquitin-binding enzyme E2C (UBE2C) mRNA | Autophagy is inhibited and accelerates migration and invasion of lung cancer cells | [319] |
Autophagy/apoptosis | FTO | Ovarian cancer | FTO accelerates ovarian cancer cell proliferation by inhibiting apoptosis and activating autophagy | Promotes tumor proliferation | [320] |
Autophagy | METTL3 | Seminoma | Overexpression of METTL3 promotes autophagy and cisplatin resistance in tumors | Supports tumorigenesis and proliferation | [299] |
Autophagy | YTHDF1 | HCC | Hypoxia-mediated HIF-1α induces expression of YTHDF1, a m6A methylation reader, and promotes translation of autophagy-related genes ATG2A and ATG14 in a m6A methylation-dependent manner | Accelerates HCC autophagy and malignant tumorigenesis | [81] |
Apoptosis | FTO | Colorectal cancer | microRNA-96 promotes anti-apoptosis in tumor cells by regulating the AMPKα2-FTO-m6A/MYC axis | Accelerates the growth and metastasis of colorectal cancer | [321] |
Apoptosis | ALKBH5 | Pancreatic cancer | ALKBH5 activates PER1 through transcription in a m6A-YTHDF2-dependent manner | Prevents cancer progression by promoting tumor cell apoptosis | [322] |
Apoptosis | METTL14 | Pancreatic cancer | Upregulation of METTL14 mediates cisplatin resistance by activating the AMPKα/ERK1/2/mTOR pathway to reduce autophagy and apoptosis | Promotes tumor progression | [233] |
Apoptosis | METTL3 | Colorectal cancer | METTL3 activates the glycolytic pathway and prevents tumor cell apoptosis by stabilizing the transcriptional translation of this gene | Promotes tumor proliferation | [57] |
Angiogenesis | IGF2BP3 | Colon cancer | IGF2BP3 binds to mRNA of cyclin D1 (cell cycle G1/S phase checkpoint) and regulates tumor angiogenesis by reading m6A methylation in the CDS region to reduce its mRNA stability | Promotes angiogenesis and metastasis in colon cancer | [192] |
Angiogenesis | YTHDF3 | Breast cancer | YTHDF3 induces the translation of m6A-enriched gene transcripts | Promotes breast cancer cell metastasis and invasion | [201] |
Angiogenesis | YTHDF2 | HCC | YTHDF2 processes the decay of m6A-containing interleukin 11 (IL11) and serpin family E member 2 (SERPINE2) mRNAs | Reduction of YTHDF2 contributes to angiogenesis and supports tumor metastasis | [195] |
Angiogenesis | METTL3 | Gastric cancer | P300-mediated activation of H3K27 acetylation in the METTL3 promoter induces METTL3 transcription, which stimulates m6A methylation of HDGF mRNA | Accelerates progression of gastric cancer | [197] |
Drug resistance | METTL3 | Lung cancer | Regulation of MALAT1-miR-1914-3p-YAP axis | Induces drug resistance and metastasis in lung cancer cells | [167] |
Drug resistance | ALKBH5 | Ovarian cancer | Overexpression of the ALKBH5-HOXA10 loop activates the JAK2/STAT3 signaling pathway | Induces cisplatin resistance in ovarian cancer | [323] |
Drug resistance | METTL3 | HCC | m6A methylation mediates autophagy in HCC via FOXO3 | Promotes HCC sorafenib resistance | [202] |
Drug resistance | YTHDF1 | Colorectal cancer | YTHDF1 promotes cisplatin resistance by reprogramming GLS1-glutamine metabolism in colorectal cancer | Inhibits tumor cell death | [95] |
EMT | METTL3 | Leukemia | N6-methyladenosine regulates TGFβ1 expression and secretion to affect epithelial-mesenchymal transition of cancer cells | Promotes tumor progression | [324] |
EMT | METTL3 | Gastric cancer | METTL3 enhances the stability of ZMYM1 mRNA through m6A modification, which, in turn, promotes EMT by recruiting the CtBP/LSD1/CoREST complex to bind and mediate repression of the E-calmodulin promoter | Promotes gastric cancer metastasis | [325] |
EMT | YTHDF1/METTL3 | HCC | METTL3 and YTHDF1 mediate Snail mRNA translation to enhance EMT | Promotes tumor metastasis | [326] |
EMT | METTL3 | Lung cancer | The m6A methyltransferase METTL3 contributes to Transforming Growth Factor-beta-induced epithelial-mesenchymal transition of lung cancer cells through regulation of JUNB | Promotes tumor metastasis | [327] |
EMT | METTL3 | Ovarian cancer | METTL3 promotes EMT by regulating AXL translation | Promotes growth and invasion of ovarian cancer | [328] |