Table 3 m6A methylation in tumor glycolysis
From: m6A-regulated tumor glycolysis: new advances in epigenetics and metabolism
Cancer type | Regulator | Function | Result | Ref |
|---|---|---|---|---|
Colorectal cancer | METTL3, IGF2BP2, IGF2BP3 | METTL3, IGF2BP2 and IGF2BP3 jointly promote the expression of HK2 and GLUT1 | Improve the glycolysis and proliferation of CRC | [108] |
VIRMA | VIRMA up-regulates the level of HK2 mRNA and improves its mRNA stability | Accelerate glycolysis and induce malignant phenotype of CRC | [109] | |
METTL3, YTHDF1 | PNN mRNA undergoes m6A modification under the action of METTL3 and improves stability by binding to YTHDF1 | Promoting glycolysis and proliferation of colon cancer | [111] | |
WTAP, YTHDF1 | WTAP and YTHDF1 enhance the stability of FOXP3 mRNA in an m6A-dependent manner | Promoting glycolysis and proliferation of colon adenocarcinoma | [112] | |
IGF2BP2 | LINRIS influences tumor glycolysis by modulating the IGF2BP2/MYC axis | Improve the glycolysis and proliferation of CRC | [113] | |
METTL3, IGF2BP2 | PTTG3P is methylated under the action of METTL3 and combines with IGF2BP2 to obtain higher stability | Improve the glycolysis and proliferation of CRC | [114] | |
IMP2 | IMP2 increases the stability of ZFAS1 RNA in an m6A-dependent manner. In turn, ZFAS1 can enhance the activity of OLA1 | Improve the glycolysis of CRC | [115] | |
METTL14, YTHDF2 | METTL14 and YTHDF2 promote the processing maturity of pri-miR-6769b and pri-miR-499a, and ultimately reduce the expression of GLUT3 and PGAM1 | Inhibiting the aerobic glycolysis and malignant phenotype of p53 WT CRC cells | [116] | |
Lung cancer | METTL3 | LncRNA ABHD11-AS1 promotes aerobic glycolysis of NSCLC through ABHD11‐AS1/EZH2/KLF4 axis | Improve the glycolysis of NSCLC | [117] |
METTL3, YTHDF1 | DLGAP1-AS2 promotes the expression of c-MYC mRNA in an m6A-dependent manner | Improve the glycolysis and proliferation of lung cancer | [118] | |
METTL3, ALKBH5, YTHDF1 | METTL3, ALKBH5, and YTHDF1 act on ENO1 mRNA to regulate ENO1 expression | Improve the glycolysis of LUAD | [119] | |
FTO, YTHDF1 | The decreased expression of FTO can increase the m6A modification in c-MYC mRNA. After that, under the action of YTHDF1, the expression of c-MYC increased | Improve the glycolysis and proliferation of LUAD | [121] | |
Breast cancer | WTAP | IL1β and TNFα secreted by C5aR1 positive neutrophils can act on the downstream ERK1/2-WTAP-ENO1 signal axis and promote the expression of ENO1 | Improve the glycolysis of Breast cancer cells | [122] |
METTL3, YTHDF2 | METTL3/LATS1/YTHDF2 axis inhibit the YAP/TAZ axis | Promote glycolysis and tumorigenesis of Breast cancer | [123] | |
YTHDF1 | Under hypoxia, the transcription of HIF-1α increases, and the expression of PKM2 in cancer cells increases through HIF-1α/miR-16-5p/YTHDF1/PKM2 axis | Improve the genesis and metastasis of Breast cancer | [124] | |
Esophageal cancer | YTHDF1 | HCP5 can enhance the binding of YTHDF1 and m6A-modified HK2 mRNA, thus improving the stability of HK2 mRNA | Improve the glycolysis and malignant phenotype of ESCC | [127] |
METTL3, METTL14, YTHDF | APC mRNA degrades under the joint action of METTL3, METTL14 and YTHDF. Therefore, the regulatory effect of APC on WNT/β-catenin pathway is weakened | Improve the aerobic glycolysis and development of ESCC | [128] | |
Liver cancer | YTHDF3 | YTHDF3 inhibits the degradation of PFKL mRNA by m6A modification | Promote the growth and lung metastasis of HCC | [129] |
ALKBH5 | UBR7 activates the Keap1/Nrf2/Bach1/HK2 axis to reduce the content of HK2 in hepatoma cells. Besides, UBR7 expression is regulated by ALKBH5 | Inhibit the glycolysis and proliferation of HCC | [130] | |
METTL14 | Mettl14/USP48/SIRT6 axis has the function of inhibiting liver cancer | Inhibit the glycolysis of HCC | [131] | |
METTL3, IGF2BP1 | Under the action of METTL3 and IGF2BP1, LNCAROD can increase the level of PKM2 through LNCAROD/PKM2 axis | Induce the glycolysis, proliferation and invasion of HCC | [132] | |
METTL3 | HBXIP can activate downstream glycolytic enzymes through METTL3/HIF-1α axis | Promote glycolysis and improve the malignancy of HCC | [133] | |
Gastric cancer | METTL3, IGF2BP3 | The expression of HDGF is increased under the action of METTL3 and IGF2BP3. After binding with the promoters of GLUT4 and ENO2, the content of glycolytic enzyme in cells is increased | Promote glycolysis, proliferation and liver metastasis of GC | [134] |
METTL3, IGF2BP1 | METTL3 and IGF2BP1 increase the stability of NDUFA4 mRNA and promote the expression of NDUFA4 | Improve the glycolysis and proliferation of GC | [135] | |
WTAP | WTAP prolongs the half-life of HK2 mRNA | Improve the glycolysis and proliferation of GC | [136] | |
VIRMA | LINC00958 degrades less under the action of VIRMA, thus promoting the expression of GLUT1 mRNA | Promote glycolysis of GC | [137] | |
IGF2BP3 | IGF2BP3 and LIN28B can recognize and bind the m6A site of c-MYC mRNA and promote glycolysis of GC | Promote the proliferation, migration and glycolysis of GC | [138] | |
IGF2BP1 | The stability of c-MYC mRNA modified with m6A is greatly improved after binding to IGF2BP1 and LIN28B | Promotes the development of gastric cancer | [139] | |
METTL14 | The stability of LHPP mRNA was enhanced after METTL14-mediated methylation. After that, LHPP inhibited glycolysis of GC by regulating WNT pathway | Inhibit the glycolysis and proliferation of GC | [140] | |
FTO, YTHDF2 | FTO can reduce the binding of YTHDF2 to the m6A site on PRKAA1 mRNA, increase its stability | Inhibit glycolysis of cancer cells and promote apoptosis | [141] | |
Pancreatic cancer | YTHDF3 | The stability of methylated DICER1-AS1 combined with YTHDF3 decreased, and the ability to promote the maturation of miR-5586-5p decreased. Therefore, the expression of glycolytic genes increases | Promote glycolysis, proliferation and metastasis of pancreatic cancer | [142] |
METTL3, IGF2BP3 | Linc-UROD is modified with m6A under the action of METTL3, and its stability is enhanced after binding with IGF2BP3. Linc-UROD can prevent ENO1 and PKM from being degraded by proteasome | Promote the glycolysis and invasion ability of pancreatic cancer | [143] | |
YTHDC1 | miR-30d is positively correlated with YTHDC1. Besides, miR-30d acts directly with the transcription factor RUNX1 to reduce the expression of GLUT1 and HK1 genes | Inhibit the genesis and glycolysis of pancreatic tumors | [144] | |
METTL3 | METTL3 promoted the expression of HK2 in an m6A-dependent manner | Promote the glycolysis and PNI of PDAC cells | [145] | |
Cervical carcinoma | METTL3, YTHDF1 | METTL3 modifies HK2 mRNA with m6A at the 3’UTR end of HK2 mRNA, and can also recruit YTHDF1 to combine with HK2 mRNA to improve the stability of HK2 mRNA | Promote the aerobic glycolysis of cervical cancer | [146] |
METTL3, IGF2BP3, YTHDF1 | METTL3 can catalyze m6A modification at the 5’UTR of PDK4 mRNA. After that, PDK4 and IGF2BP3 combine to obtain stronger stability, or combine with YTHDF1/eEF-2 complex to improve translation efficiency | Promote glycolysis and proliferation of cancer cells | [147] | |
IGF2BP2 | E6/E7 protein produced by HPV can promote the expression of IGF2BP2, make it recognize and bind more m6A-MYC mRNA | Promote the proliferation and glycolysis of cervical cancer cells | [149] | |
Renal carcinoma | METTL14 | The transcription factor BPTF can enhance the glycolysis of cancer cells to drive the distant metastasis of renal cell carcinoma. However, this process is inhibited by METTL14 | Inhibit the glycolysis and the distant metastasis of renal cell carcinoma | [150] |
METTL3 | MTHFD2 has a positive regulatory effect on METTL3-induced HIF-2α mRNA methylation | Promote the glycolysis and proliferation of cancer cells | [151] | |
IGF2BP1 | IGF2BP1 directly binds to the m6A modification site on LDHA mRNA, thereby enhancing the stability of LDHA mRNA | Promoting glycolysis and malignant phenotype of renal cell carcinoma | [152] | |
Osteosarcoma | RBM15 | Circ-CTNNB1 directly combines with RBM15 to increase the expression of glycolytic enzyme in an m6A-dependent manner | Promote glycolysis and development of osteosarcoma | [153] |
YTHDF3 | The stability of m6A-modified PGK1 mRNA was improved after binding to YTHDF3 | Promote glycolysis and proliferation of osteosarcoma cells | [154] | |
Oral squamous cell carcinoma | IGF2BP3 | m6A-circFOXK2 and IGF2BP3 act synergistically on GLUT1 mRNA to improve its stability | Promote glycolysis and transfer of OSSC | [156] |
Glioblastoma | IGF2BP2 | IGF2BP2 can recognize and combine methylated CASC9 to enhance the stability of CASC9. The complex can also improve the stability of HK2 mRNA | Promote glycolysis of GBM | [157] |
Cholangiocarcinoma | METTL3 | Under the action of METTL3, the stability and expression of AKR1B10 mRNA are improved | Promote the growth and glycolysis of cholangiocarcinoma | [158] |
Thyroid papillary carcinoma | FTO, IGF2BP2 | APOE induces the expression of glycolytic enzymes through the IL-6/JAK2/STAT3 signal pathway. However, FTO can inhibit the expression of APOE | Inhibit the glycolysis and proliferation of thyroid papillary carcinoma | [159] |
Prostate cancer | METTL3 | The stability of lncRNA SNHG7 was improved under the action of METTL3. High expression of SNHG7 can activate the downstream SRSF1/c-MYC/glycolytic axis | Promote the glycolysis and development of prostate cancer | [160] |
Ovarian cancer | WTAP | In hypoxic environments, the activation of the HIF-1α/WTAP/miR-200/HK2 axis increases | Enhances the glycolysis and proliferation of ovarian cancer | [161] |