YTHDF1-Mediated mA Methylation of GLUT1 Promotes Progress and Suppresses Propranolol Sensitivity in Infantile Hemangioma.

Early intervention for infantile hemangioma (IH) typically involves the use of the first-line drug propranolol, which can be taken orally or applied topically. However, approximately 10% of patients develop resistance, highlighting the need to elucidate the underlying molecular mechanisms. This study found that the expression of glucose transporter 1 (GLUT1) was significantly increased in IH tissues. Knockdown of GLUT1 significantly inhibited the cell viability, colony formation, and angiogenesis of HemEC cells. Moreover, high GLUT1 levels caused insensitivity to propranolol treatment in IH as HemEC cells showed few significant changes to intracellular GLUT1 protein expression and glycolysis level upon treatment with propranolol, while overexpression of GLUT1 promoted colony formation and increased the IC value of HemEC cells with propranolol treatment. The YT521-B homology domain family protein 1 (YTHDF1), an mA reader in mRNA, was significantly increased in IH tissues compared with normal adjacent tissues. MeRIP-qPCR results showed that YTHDF1 binds to GLUT1 mRNA and promoted its stability and translation efficiency, resulting in GLUT1 upregulation, thereby inhibiting the sensitivity of IH to propranolol. Additionally, YTHDF1 overexpression promoted the ability of colony formation and increased the IC value of HemEC cells with propranolol treatment. However, this promotion was reversed by knockdown of GLUT1. Collectively, our results demonstrated that YTHDF1-mediated mA recognition of GLUT1 is vital in IH development and propranolol insensitivity. The YTHDF1/GLUT1 axis may serve as a potential target for inhibiting IH progression from aggravating and overcoming propranolol resistance in IH.