Table 4 m6A affects tumor therapy by regulating tumor glycolysis

Chemotherapy

ALKBH5

The low expression of ALKBH5 cannot reduce the m6A modification level of CK2α mRNA, which increases the stability of CK2α mRNA, prolongs its half-life

Reduce the sensitivity of bladder cancer cells to cisplatin chemotherapy

[163]

ZC3H13

The m6A modification induced by methyltransferase ZC3H13 can reduce the stability of PKM2 mRNA, inhibit the glycolysis of liver cancer cells

Make HCC more sensitive to cisplatin treatment

[164]

METTL3, IGF2BP1

Under the action of METTL3 and IGF2BP1, LNCAROD can promote the glycolysis and malignancy of HCC

Induce HCC resistance to 5-FU

[132]

METTL3, IGF3BP3, YTHDF1

METTL3 can induce HIF-1α mRNA methylation and recruit IGF3BP3 to improve its stability, thus improving the transcription level of LDHA. METTL3 also catalyzes m6A modification in the CDS region of LDHA mRNA and recruits YTHDF1 to bind with m6A-LDHA mRNA

Induce CRC resistance to 5-FU

[166]

FTO

JPX can directly bind to PDK1 mRNA and can also enhance FTO-mediated demethylation of PDK1 mRNA, both of which improve the stability of PDK1 mRNA

Induce GBM resistance to TMZ

[168]

ALKBH5

Aerobic glycolysis induces the release of exosomal circ_0072083, thus promoting the expression of NANGO mediated by ALKBH5

Induce GBM resistance to TMZ

[169]

METTL3, IGF2BP2

Under the action of METTL3 and IGF2BP2, the expression of WWP2 increases and promotes liver cancer glycolysis through the WWP2/AKT axis

Induce HCC resistance to doxorubicin

[171]

FTO

LncRNA HOTAIR can collaborate with FTO to remove the methylation modification of HK2 mRNA, thereby increasing the expression of HK2

Sevoflurane can inhibit HOTAIR and FTO mediated promotion of liver cancer glycolysis

[173]

Immunotherapy

YTHDF1

CircRHBDD1 can recruit YTHDF1 and combine with m6A modified PIK3R1 mRNA, improve the translation level of PIK3R1 mRNA, promote the glycolysis of liver cancer cells through subsequent PI3K/AKT signal transduction pathway

Make HCC resistant to anti-PD-L1 treatment

[174]

METTL3, IGF2BP3, YTHDC1

During the expression of NCAPH, IGF2BP3 and YTHDC1 regulate the stability of NCAPH mRNA and nuclear output in an m6A-dependent manner. The highly expressed NCAPH can promote the glycolysis of cancer cells and increase the expression of PD-L1 by stabilizing the β-catenin protein

Induce resistance to anti-PD-1 therapy

[175]

METTL3, IGF2BP2

m6A modified circQSOX1 can recruit miR-326 and miR-330-5p to increase the expression of PGAM1, enhance the glycolysis of CRC and increase the production of lactate

Reduce the anti-CTLA-4 therapeutic effect

[176]

FTO, ALKBH5

GNRa-CSP12 can destroy the balance of intracellular Fe²⁺/Fe³⁺, inactivate the Fe²⁺-dependent demethylase FTO and ALKBH5. This can reduce the stability of GLUT3 and PKM transcripts that mediate glycolysis and immune checkpoint pathway

Enhance the therapeutic effect of PD-L1 checkpoint blockade

[177]

Targeted therapy

ALKBH5, YTHDF2

ALKBH5 removes the m6A modification of GLUT4 mRNA in cancer cells, and recruits YTHDF2 to combine with GLUT4 mRNA to enhance its stability, leading to increased glycolysis of breast cancer cells

Induce the resistance of breast cancer to HER2 targeted therapy

[178]

m6A inhibitor

FTO

R-2HG competitively inhibits the enzymatic activity of FTO, reduces the stability and expression of PFKP and LDHB transcripts

Inhibit glycolysis and hinder the proliferation of AML

[201]

FTO

Dac51 effectively inhibits the enzymatic activity of FTO and reduces the stability and expression of JunB and C/EBPβ transcripts

Inhibit glycolysis and hinder the proliferation of melanoma

[202]