Abstract
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 explored their association with clinical and inflammatory parameters of asthma.
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.
In total 78 differentially expressed miRNAs were identified in bronchial biopsies of asthma patients compared to controls, of which 60 remained differentially expressed after controlling for smoke 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 and 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. Collectively, we identified miR-125b-5p, miR-223-3p and miR-26a-5p, as potential regulators that could contribute to the pathogenesis of asthma.
Footnotes
This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.
Conflict of interest: Dr. Roffel has nothing to disclose.
Conflict of interest: Dr. Boudewijn has nothing to disclose.
Conflict of interest: Dr. van Nijnatten has nothing to disclose.
Conflict of interest: Dr. Faiz has nothing to disclose.
Conflict of interest: Dr. Vermeulen has nothing to disclose.
Conflict of interest: Dr. Van Oosterhout reports and Van Oosterhout owns GSK shares.
Conflict of interest: Dr. Affleck reports and I am an employee of GlaxoSmithKline but have no conflict of interest related to this manuscript.
Conflict of interest: Dr. Timens reports personal fees from Roche Diagnostics/Ventana, personal fees from Merck Sharp Dohme, personal fees from Bristol-Myers-Squibb, personal fees from Diaceutics, outside the submitted work.
Conflict of interest: Dr. Bracke has nothing to disclose.
Conflict of interest: Dr. Maes reports grants from Ghent University, grants from Fund for Scientific Research in Flanders, during the conduct of the study; personal fees from GlaxoSmithKline, grants from Chiesi, outside the submitted work; and is shareholder from Oryzon Genomics and Mendelion Lifesciences SL.
Conflict of interest: Dr. Heijink has nothing to disclose.
Conflict of interest: Dr. Brandsma has nothing to disclose.
Conflict of interest: Dr. van den Berge reports research grants to Institution from GlaxoSmithKline. Sanofi, Novartis, Genentech, Roche, outside the submitted work.
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- Received May 5, 2021.
- Accepted July 30, 2021.
- Copyright ©The authors 2021. For reproduction rights and permissions contact permissions{at}ersnet.org
