
This study investigated the relationship between N6-methyladenosine (m6A) RNA methylation, specifically the enzyme METTL3, and glucose metabolism in intrahepatic cholangiocarcinoma (ICC) progression. The researchers found that METTL3 was highly expressed in ICC, which correlated with poor prognosis. METTL3 upregulated m6A modification of NFAT5, leading to the recruitment of IGF2BP1 and stabilization of NFAT5 mRNA. This resulted in increased expression of gluconeogenesis-related genes GLUT1 and PGK1, promoting aerobic glycolysis, proliferation, and tumor metastasis in ICC. Additionally, higher METTL3 expression was observed in ICC patients with activated glucose metabolism. The study also identified STM2457, a potent METTL3 inhibitor, as a potential therapeutic strategy in ICC treatment, particularly in combination with gemcitabine.
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