Integrated miRNA-mRNA network analysis identifies miR-182-5p as a potential regulator in COPD pathogenesis.

Introduction: Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality worldwide and currently lacks effective disease-modifying therapies. Extracellular vesicles (EVs) are key mediators of intercellular communication and transport biologically active cargo, including microRNAs (miRNAs). We previously identified 8 differentially expressed EV miRNA (miR-223-3p, miR-2110, miR-182-5p, miR-200b-5p, miR-625-3p, miR-204-5p, miR-138-5p and miR-338-3p) that were differentially expressed in individuals with COPD compared with healthy volunteer ex-smoker controls (HV-ES). This study aimed to identify miRNA-mRNA interactions in diseased lung epithelium that may contribute to COPD pathogenesis. Methods: Gene expression was quantified by RNA sequencing of epithelial brushings obtained from 24 subjects with COPD and 20 HV-ES. Results: A total of 191 genes were differentially expressed in epithelial brushings from subjects with COPD compared with HV-ES. Discussion: These findings highlight a potential role for EV-derived miRNA-mRNA regulatory networks in COPD pathogenesis, with miR-182-5p emerging as a putative regulator within this network. While exploratory analyses suggested possible associations with metabolic and immune-related pathways, these did not withstand multiple testing correction and should therefore be interpreted as hypothesis-generating. These findings support further mechanistic investigation of EV-derived miRNA-mRNA regulatory networks in COPD and may help inform future translational studies exploring their biological relevance.