METTL3 promotes m⁶A-dependent maturation of pri-miRNA-150 to enhance ESCC tumor proliferation

　　Objecive Exploring the regulatory mechanism of METTL3-mediated m⁶A methylation in promoting pri-miR-150 maturation in esophageal squamous cell carcinoma.
　　Methods Quantitative real-time PCR (qRT-PCR) , western blot were used to detect the expression of METTL3, pri-miR-105, miR-150 and MYB in esophageal squamous cell carcinoma (ESCC) cell lines; lentiviral transfection and cell proliferation assays were applied to explore the role of METTL3 in ESCC cell proliferation. RIP (RNA immunoprecipitation) and Co-IP (co-immunoprecipitation) assays were used to confirm that METTL3 binds DGCR8 and regulates pri-miR-105 processing and maturation in an m⁶A methylation-dependent manner; luciferase reporter assays were utilized to map the direct binding sites between miR-150 and MYB.Colony formation and CCK-8 assays confirmed that miR-150 functions in METTL3-induced ESCC cell proliferation.
　　Results Our data demonstrated that METTL3 expression was significantly upregulated in esophageal squamous cell carcinoma (ESCC) tissues and corresponding cell lines. METTL3 knockdown or overexpression suppressed or enhanced ESCC cell proliferation, respectively. METTL3 mediates miR-150 processing and maturation via DGCR8, and miR-150 rescues METTL3-induced ESCC cell proliferation by targeting the MYB transcription factor.
　　Conclusions This study is the first to demonstrate that METTL3 promotes pri-miR-150 processing and maturation in an m⁶A methylation-dependent manner by interacting with DGCR8, thereby enhancing ESCC cell proliferation and providing novel insights into ESCC diagnosis and treatment.