Table 2 m6A in cancer metabolic pathways

Glucose metabolism

GLUT1

Gastric cancer

KIAA1429 catalyzes long noncoding RNA Linc00958 which stabilizes GLUT1 in a m6A-dependent manner, thereby augmenting the effect of aerobic glycolysis.

[72]

GLUT1

Colorectal cancer

METTL3 directly targets the m6A-GLUT1-mTORC1 axis to prompt glucose uptake and lactate production.

[73]

GLUT4

Breast cancer

ALKBH5 targets at GLUT4 mRNA, promotes its demethylation and stability, and augments glycolysis.

[74]

HK2

Cervical cancer

METTL3 links to the 3’-Untranslated Region of HK2 mRNA and recruits YTHDF1 to ensure HK2 steadiness, finally facilitating proliferation and aerobic glycolysis.

[75]

HK2

Pancreatic cancer

Glutamate upregulates METTL3 and further promotes HK2 in m6A dependent manner and ultimately enhances glycolysis.

[76]

HK2

Gastric cancer

WTAP binds the 3’-UTR m6A site of HK2, enhances its stability and augments the Warburg effect.

[77]

HK2, GLUT1

Colorectal cancer

METTL3 stabilizes HK2 and GLUT1 expression via IGF2BP2 or IGF2BP2/3 mechanism, and activate the subsequent aerobic glycolysis pathway.

[79]

HK2

Colorectal cancer

KIAA1429 increases HK2 level so as to boosts aerobic glycolysis.

[80]

HK2

Esophageal squamous cell carcinoma

YTHDF1 binds to HK2 mRNA to enhance its stability and thereby promotes esophageal squamous cell carcinoma.

[81]

ENO1

Breast cancer

C5aR1-positive neutrophils secrete TNF-α, activate ERK1/2 signaling, phosphorylate WTAP and ensure its steadiness, thereby augmenting the level of ENO1 m6A methylation to facilitate glycolysis.

[82]

ENO1

Lung adenocarcinoma

The up-regulation of METTL3 and down-regulation of ALKBH5 lead to the elevated m6A level of ENO1 and stimulate glycolysis.

[83]

PKM2

Hepatocellular carcinoma

FTO induces the demethylation of PKM2 mRNA to fuel translation.

[84]

PKM2

Breast cancer

YTHDF2 enhances PKM2 and subsequently augments aerobic glycolysis.

[85]

LDHA

Colorectal cancer

METTL3 up-regulates the level of LDHA to trigger aerobic glycolysis.

[87]

LDHA

Clear cell renal cell carcinoma

IGF2BP1 recognizes LDHA m6A sites, increases LDHA mRNA stability and accelerates aerobic glycolysis.

[88]

LDHB

Leukemia

R-2HG abrogates the upregulation of LDHB gene expression through FTO demethylation and thereby suppresses glycolysis.

[89]

CK2α

Bladder cancer

ALKBH5 mediates glycolysis by attenuating the stability of CK2α in m6A-dependent manner.

[90]

PDK1

Glioblastoma

LncRNA just proximal to XIST (JPX) enhances FTO-mediated PDK1 mRNA demethylation to facilitate glycolysis.

[91]

PDK4

Cervical cancer, Liver cancer

YTHDF1 and IGF2BP3 positively modulates glycolysis by binding with PDK4.

[92]

BPTF

Renal cell carcinoma

METTL14-mediated m6A modification downregulates the BPTF mRNA stability and induces glycolytic reprogramming.

[93]

MYC

Cervical cancer

Human papillomavirus (HPV) regulates IGF2BP2 to stabilize the expression of MYC, thus promoting aerobic glycolysis.

[94]

MYC

Colorectal cancer

Long intergenic noncoding RNA for IGF2BP2 stability (LINRIS) augments the effect of IGF2BP2, and thereby promotes MYC-mediated glycolysis.

[95]

MYC

Non-small cell lung cancer

YTHDF1 and m6A-modified lncRNA discs large homolog associated protein 1 (DLGAP1) promotes glycolysis by stabilizing c-myc mRNA.

[96]

MYC

Gastric cancer

IGF2BP1 stabilizes c-myc mRNA and speeds up aerobic glycolysis.

[97]

HIF-1α

Hepatocellular carcinoma

HBXIP increases m6A abundance of HIF-1α via METTL3, thus driving glycolysis.

[98]

HIF-2α

Renal cell carcinoma

Methylenetetrahydrofolate Dehydrogenase 2 (MTHFD2) controls the level of m6A in HIF-2α mRNA which promotes the aerobic glycolysis.

[99]

HIF-1α

Renal cancer

YTHDF2 together with PBRM1 up-regulates HIF-1α to promotes cancer progression.

[100]

G6PD

Colorectal cancer

YTHDF2 degrades circ-0003215 and further modulates the level of DLG4, which blocks the PPP via the ubiquitination of G6PD.

[101]

G6PD

Colorectal cancer

METTL3 degradation promotes the stability of LINC01615, upregulates the level of G6PD by enhancing G6PD pre-mRNA splicing and further activates PPP.

[102]

G6PD

Glioma

ALKBH5 facilitates the mRNA stability of G6PD, enhances its translation and finally stimulates cell proliferation.

[103]

6PGD

Lung cancer

By recognizing m6A site on 6PGD, YTHDF2 directly binds with 6PGD, promotes its expression and facilitates the progress of lung cancer.

[104]

Lipid metabolism

ACLY, ACC1

Esophageal cancer

HNRNPA2B1 up-regulates ACLY and ACC1 gene expression to fuel fatty acid metabolism.

[113]

ACLY, SCD1

Hepatocellular carcinoma

METTL3/14 targets at ACLY and SCD1, increases their expression and promotes lipid metabolism.

[114]

FASN

Hepatocellular carcinoma

FTO ensures the stability of FASN mRNA and prevents mRNA degradation to positively influence lipid metabolism.

[115]

SREBP

Hepatocellular carcinoma

FTO acts on SREBP1C to affect the downstream effectors FASN, SCD, ACC1, DGAT2, CIDEC and CPT1, promoting lipid synthesis, lipid store and fatty acid oxidation eventually.

[116,117,118,119,120]

ACSL4

Hepatocellular carcinoma

METTL5 targets at 18 S rRNA, impairs 80 S ribosome, reduces the level of proteins related to fatty acid metabolism. ACSL4 regulates the role of METTL5 in fatty acid metabolism and thus facilitates cancer progression.

[121]

ACC1

Cervical squamous cell carcinoma

ALKBH5 and IGF2BP1 target at SIRT3, lower its stability, consequently inhibit ACC1 deacetylation and lipid metabolism.

[122]

Amino acid metabolism

SLC1A5

Clear cell renal cell carcinoma

FTO and VHL can indirectly target SLC1A5 in the downstream so as to promote metabolic recombination.

[126]

GLS

Colon cancer

YTHDF1 targets the 3’ UTR of GLS1 to boost the function of GLS1 and facilitate glutamine metabolism.

[127]

MYC, GPT2, and SLC1A5

Acute myeloid leukemia

IGF2BP2 targets at MYC, GPT2, and SLC1A5 and enhances glutamine metabolism.

[128]

BCAT1, BCAT2

Acute myeloid leukemia

METTL16 affect branched-chain amino acid metabolism in AML by upregulating the expression of BCAT1 and BCAT2 via m6A modification.

[129]

Mitochondrial metabolism

PGC-1α

Clear cell renal cell carcinoma

FTO decreases the abundance of m6A in PGC-1α mRNA transcripts, increases its expression and recovers mitochondrial activity.

[130]

AK4

Breast cancer

METTL3 selectively targets the 5’ UTR of AK4 mRNA, which ultimately inhibits mitochondrial apoptosis.

[132]

TLR4

multiple myeloma

HNRNPA2B1 enriches at the m6A sites of TLR4, thus enhancing mitochondrial metabolism.

[133]