Inhibitory effects of METTL3 on airway smooth muscle cell proliferation and migration via lncRNA GAS5/miR-29c-3p/VAMP2 axis.

Objective: Asthma development is significantly influenced by the abnormal proliferation and migration of human airway smooth muscle cells (HASMCs). The aim of this study was to investigate the role and molecular mechanisms of the m6A methyltransferase METTL3 in platelet-derived growth factor BB (PDGF-BB)-treated HASMCs. Methods: An in vitro model of HASMCs stimulation was constructed by PDGF-BB. Proliferation, migration, and levels of inflammatory factors of HASMCs were detected by CCK-8, Transwell assay, and ELISA, respectively. m6A modification sites in GAS5 were predicted using WHISTLE. m6A methylation level in GAS5 was detected by MeRIP-qPCR. The RNA stability of GAS5 was assessed by RNA decay assay. Targeted binding sites between miR-29c-3p and GAS5 or VAMP2 were predicted using starBase, and their targeting relationship was verified by dual-luciferase reporter assay. Results: METTL3 levels were decreased in PDGF-BB-induced HASMCs. Enhancing METTL3 expression in HASMCs inhibited PDGF-BB-induced proliferation, migration, and inflammation. METTL3-mediated m6A methylation decreased GAS5 stability, thereby inhibiting GAS5 expression. GAS5 targeted miR-29c-3p and regulated VAMP2 expression. In PDGF-BB-treated HASMCs, enhancing VAMP2 mitigated the effect of METTL3 upregulation. Conclusion: METTL3 inhibits HASMC proliferation, migration, and inflammation in asthma by regulating the GAS5/miR-29c-3p/VAMP2 axis.