Mirjam P Roffel1,2,3, Ilse M Boudewijn2,4, Jos L L van Nijnatten1,2,5, Alen Faiz1,2,5, Corneel J Vermeulen2,4, Antoon J van Oosterhout6, Karen Affleck7, Wim Timens1,2, Ken R Bracke3, Tania Maes3, Irene H Heijink1,2,4, Corry-Anke Brandsma1,2,8, Maarten van den Berge9,4,8. 1. Dept of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. 2. Groningen Research Institute for Asthma and COPD, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. 3. Dept of Respiratory Medicine, Laboratory for Translational Research in Obstructive Pulmonary Diseases, Ghent University, University Hospital Ghent, Ghent, Belgium. 4. Dept of Pulmonology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. 5. Faculty of Science, Respiratory Bioinformatics and Molecular Biology (RBMB), University of Technology Sydney, Sydney, Australia. 6. Allergic Inflammation Discovery Performance Unit, GlaxoSmithKline, Stevenage, UK. 7. Adaptive Immunity Research Unit, GlaxoSmithKline, Stevenage, UK. 8. Both C-A. Brandsma and M. van den Berge are senior authors and contributed equally to this work. 9. Groningen Research Institute for Asthma and COPD, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands m.van.den.berge@umcg.nl.
Abstract
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.
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.