METTL1 drives glioma progression by promoting N7-methylguanosine (m7G) modification of glycolysis-related enzyme PGK1.

Glioma is a common brain malignancy with a poor prognosis. N7-methylguanosine (m7G) modification is involved in cancer progression, and methyltransferase 1 (METTL1) is a m7G methyltransferase. Here, we aimed to study the role of METTL1 in glioma and the potential mechanism. The proliferation of glioma cells was evaluated using cell counting kit-8 and 5-ethynyl-2'-deoxyuridine (EdU) assays, and the glycolysis was assessed using glucose uptake and lactate content kits and seahorse analysis. The regulation of METTL1 on phosphoglycerate kinase 1 (PGK1) was analyzed using methylated RNA immunoprecipitation, RNA immunoprecipitation, quantitative real-time polymerase chain reaction, western blotting, and RNA stability assay. The results showed that METTL1 expression was upregulated in glioma tissues and cells. Silencing of METTL1 inhibited the proliferation and glycolysis of glioma cells and impeded tumor growth in mice. Moreover, METTL1 knockdown suppressed internal m7G modification of PGK1 and decreased its half-life. PGK1 overexpression counteracted the inhibition of glioma cell proliferation and glycolysis induced by METTL1 knockdown. In conclusion, METTL1 functions as an oncogene to accelerate glioma progression by promoting m7G modification of PGK1, providing a potential therapeutic target for glioma.