MicroRNA profiling in bronchial biopsies identifies altered expression in asthma and high levels of allergen-modulated epithelial microRNAs

Background and aim: MicroRNAs (miRNAs) are important post-transcriptional regulators of immune responses and implicated in asthma pathogenesis. We aimed to determine miRNA profiles in bronchial biopsies and bronchial epithelial cells (BECs) from healthy and asthmatic individuals and investigate the effect of the asthma-associated allergen house dust mite (HDM) on epithelial miRNA expression. Methods: RNA extracted from bronchial biopsies of 12 well-characterized subjects (n=6/group) from the West Sweden Asthma Study (WSAS) cohort was subjected to profiling of ∼800 miRNAs using the nCounter Human v3 miRNA assay (NanoString Technologies). miRNA expression was similarly assessed in cell lysates from air-liquid interface cultures of primary human BECs treated with or without 200 µg/ml HDM for 24h. Results: A total of 149 miRNAs were identified in bronchial biopsies from all individuals and 11 of these miRNAs were differentially expressed (p<0.05) in asthmatic subjects compared to healthy controls. BECs stably expressed 187 miRNAs and HDM significantly altered the levels of six miRNAs (p<0.05), of which miR-16-5p (1.34-fold) and miR-26a-5p (1.29-fold) were among the top 30 most highly expressed miRNAs in both bronchial biopsies and BECs. Conclusion: Our data indicate a distinct miRNA profile in bronchial biopsies of asthmatic individuals and high expression of hub airway epithelial miRNAs that are modulated by allergen exposure. Further studies are needed to validate the results in more subjects and to identify immunoregulatory miRNA-mRNA networks in the airway epithelium that may be dysregulated in asthma.