Identification of asthma-associated microRNAs in bronchial biopsies.

Background: Changes in microRNA (miRNA) expression can contribute to the pathogenesis of many diseases, including asthma. We aimed to identify miRNAs that are differentially expressed between asthma patients and healthy controls, and explore their association with clinical and inflammatory parameters of asthma.
Methods: Differentially expressed miRNAs were determined by small RNA sequencing on bronchial biopsies of 79 asthma patients and 82 healthy controls using linear regression models. Differentially expressed miRNAs were associated with clinical and inflammatory asthma features. Potential miRNA-mRNA interactions were analysed using mRNA data available from the same bronchial biopsies, and enrichment of pathways was identified with Enrichr and g:Profiler.
Results: In total, 78 differentially expressed miRNAs were identified in bronchial biopsies of asthma patients compared with controls, of which 60 remained differentially expressed after controlling for smoking and inhaled corticosteroid treatment. We identified several asthma-associated miRNAs, including miR-125b-5p and miR-223-3p, based on a significant association with multiple clinical and inflammatory asthma features and their negative correlation with genes associated with the presence of asthma. The most enriched biological pathway(s) affected by miR-125b-5p and miR-223-3p were inflammatory response and cilium assembly/organisation. Of interest, we identified that lower expression of miR-26a-5p was linked to more severe eosinophilic inflammation as measured in blood, sputum as well as bronchial biopsies.
Conclusion: Collectively, we identified miR-125b-5p, miR-223-3p and miR-26a-5p as potential regulators that could contribute to the pathogenesis of asthma.
Competing Interests: Conflict of interest: M.P. Roffel has nothing to disclose. Conflict of interest: I.M. Boudewijn has nothing to disclose. Conflict of interest: J.L.L. van Nijnatten has nothing to disclose. Conflict of interest: A. Faiz has nothing to disclose. Conflict of interest: C.J. Vermeulen has nothing to disclose. Conflict of interest: A.J. van Oosterhout owns GlaxoSmithKline shares. Conflict of interest: K. Affleck is an employee of GlaxoSmithKline. Conflict of interest: W. Timens reports personal fees for consultancy from Roche Diagnostics/Ventana, Bristol-Myers-Squibb and Diaceutics, personal fees for consultancy and lectures from MSD, outside the submitted work. Conflict of interest: K.R. Bracke has nothing to disclose. Conflict of interest: T. Maes reports grants from Ghent University (BOF19-GOA-008, BOF U4 funding; 05U40516) and Fund for Scientific Research in Flanders, during the conduct of the study; personal fees for advisory board work from GlaxoSmithKline, grants from Chiesi, outside the submitted work; and is shareholder of Oryzon Genomics and Mendelion Lifesciences SL. Conflict of interest: I.H. Heijink has nothing to disclose. Conflict of interest: C-A. Brandsma has nothing to disclose. Conflict of interest: M. van den Berge reports research grants (Paid to institution) from GlaxoSmithKline, Sanofi, Novartis, Genentech and Roche, outside the submitted work.
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