Extracellular vesicles produced by airway epithelial cells from COPD patients contain miRNAs involved in cellular senescence

Background: COPD is a chronic lung inflammatory disease linked to lung aging and cellular senescence. MicroRNAs (miRNA) are 21-23 non-coding RNAs that induce post-transcriptional repression of their mRNA targets. Extracellular vesicles (EVs) carry miRNA, mRNA and proteins and play a key role in intercellular communication. Dysregulation of miRNA expression in cells and in EVs may participate in the induction and spreading of cellular senescence in COPD Aim: To compare miRNAs species encapsulated in EVs produced by small airway epithelial cells from healthy and COPD donors and their role on epithelial cells senescence Methods: Small airway epithelial cells (SAEC) from healthy donors and COPD patients were plated in submerged culture and EVs were isolated by differential ultracentrifugation of cell supernatants. Total RNAs from cells and EVs were isolated and miRNA species were analysed by miRNA sequencing Results: 13 miRNAs were significantly upregulated in EVs derived from COPD SAEC compared to healthy subjects (n=5). All miRNAs were also found upregulated in COPD SAEC compared to healthy subjects. Six miRNAs were implicated in senescence pathways: miR-100-5p (1.38 fold increase in COPD EVs), miR-424-5p (3.18-fold increase), miR-19b-3p (1.95-fold increase), miR-20a-5p (0.58-fold increase), miR-27a-3p (1.08-fold increase), miR-17-5p (0.68-fold increase) Conclusion: Our data suggest that EVs derived from COPD SAEC are enriched in miRNA involved in cellular senescence. This may contribute to COPD pathophysiology by inducing cellular senescence in adjacent cells. Further exploration of vesicular miRNAs in COPD may provide useful biomarkers and targets for therapy.