METTL14-mediated lncRNA NEAT1 promotes asthma progression by regulating the miR-302a-3p/March5 axis

Asthma is a chronic inflammatory airway disease with airway remodeling as its main pathological basis. LncRNA NEAT1 has been reported to be up-regulated in asthma, but its upstream and downstream regulatory mechanisms are unclear. This study explored the role and functional mechanism of lncRNA NEAT1 in asthma. Airway smooth muscle cells (ASMCs) isolated from the bronchial tissues of asthmatic patients and healthy volunteers were employed and transfected with an overexpression lentivirus and short hairpin lentivirus. Real-time quantitative PCR (qRT-PCR) and western blotting were used to determine the expression levels of genes. The proliferation and migration of ASMCs were evaluated, and the levels of pro-inflammatory cytokines, inflammasomes, and ROS were determined. Mitophagy was observed by transmission electron microscopy (TEM). An asthma model was established to further confirm the effects of lncRNA NEAT1 on asthma. Our results showed that lncRNA NEAT1 was highly expressed in asthma patient-derived ASMCs. LncRNA NEAT1 enhanced ASMC proliferation and migration, promoted inflammation, and inhibited mitophagy. Treatment with a mitophagy inducer reversed the effects of lncRNA NEAT1. The regulatory axis of lncRNA NEAT1/miR-302a-3p/March5 was confirmed, and lncRNA NEAT1 was found to influence ASMC function via the miR-302a-3p/March5 axis. Moreover, METTL14 was found to enhance lncRNA NEAT1 m6A modification and promote its expression, and thereby participate in the functional regulation of ASMCs. The role of lncRNA NEAT1 was also confirmed in an asthma mouse model, where it alleviated asthma pathology in lncRNA NEAT1 knockdown mice. Collectively, our present study confirmed that METTL14 mediated m6A modification of lncRNA NEAT1 and improved lncRNA NEAT1 expression, which further inhibited mitophagy and promoted asthma progression by regulating the miR-302a-3p/March5 axis. Our study elucidated the mechanism by which lncRNA NEAT1 affects airway remodeling. It also provides valuable insights into the pathogenesis of asthma, and suggests lncRNA NEAT1 as a possible biomarker for asthma.