MiRNA Expression Profile in the Airways Is Altered during Pulmonary Exacerbation in Children with Cystic Fibrosis—A Preliminary Report

Abstract

MicroRNAs are small non-coding RNAs that regulate immune response and inflammation. We assumed that miRNAs may be involved in the immune response during cystic fibrosis pulmonary exacerbations (CFPE) and that altered expression profile in the airways and blood may underlie clinical outcomes in CF pediatric patients. Methods: We included 30 pediatric patients diagnosed with cystic fibrosis. The biologic material (blood, sputum, exhaled breath condensate) was collected during pulmonary exacerbation and in stable condition. The miRNA expression profile from blood and sputum (n = 6) was done using the next-generation sequencing. For validation, selected four miRNAs were analyzed by qPCR in exosomes from sputum supernatant and exhaled breath condensate (n = 24). NGS analysis was done in Base Space, correlations of gene expression with clinical data were done in Statistica. Results: The miRNA profiling showed that four miRNAs (miR-223, miR-451a, miR-27b-3p, miR-486-5p) were significantly altered during pulmonary exacerbation in CF patients in sputum but did not differ significantly in blood. MiRNA differently expressed in exhaled breath condensate (EBC) and sputum showed correlation with clinical parameters in CFPE. Conclusion: MiRNA expression profile changes in the airways during pulmonary exacerbation in CF pediatric patients. We suggest that miRNA alterations during CFPE are restricted to the airways and strongly correlate with clinical outcome.

miR-224-5p and miR-545-5p Levels Relate to Exacerbations and Lung Function in a Pilot Study of X-Linked MicroRNA Expression in Cystic Fibrosis Monocytes

“…This miRNA was not selected by the authors for further validation by qPCR but it would be interesting to see if its expression was significantly altered in a larger cohort, including equal numbers of male/female samples in both the CF and non-CF groups, and if there are any correlations with clinical parameters. A recent study by Stachowiak et al (2020) reported a number of miRNAs from airway samples to show correlation with CF pulmonary exacerbation parameters, one of which was an X-linked miRNA, miR-223-3p. Increased levels of miR-223-3p were found in exhaled breath condensate and sputum during pulmonary exacerbation with concurrent Aspergillus infection.…”

S-RBD-modified and miR-486-5p-engineered exosomes derived from mesenchymal stem cells alleviate radiation-induced lung injury and long-term pulmonary fibrosis via suppression of ferroptosis

“…MiR-486-5p expression is decreased in the serum samples and lung tissues of patients with silicosis and idiopathic pulmonary brosis [18]. MiR-486-5p targets SMAD2, a crucial mediator of pulmonary brosis [19] and decreases pulmonary exacerbation in patients [20]. Growing evidence has indicated that miR-486-5p regulates in ammation and brosis in lung tissues [18,21].…”

Next Generation Sequencing for miRNA Detection on the Exhaled Breath Condensate: A Pilot Study

“…The low yield of miRNA from the EBC is a major obstacle, which was successfully overcome in 2 studies using the NGS technology. 22 , 24 Also, its potential for discovering previously unidentified miRNAs 21 would make it more suitable for the purposes of the project we are about to launch on detecting new molecular signatures as early biomarkers of asbestos-related health effects. Based on such assumptions, we conducted a preliminary test on male volunteers to compare of the EBC miRNA profile in the EBC to that in the plasma using 2 sequencing platforms, different in terms of cost and performance.…”