Circulating MicroRNAs: Association with Lung Function in Asthma

Abstract

BackgroundMicroRNAs are key transcriptional and network regulators previously associated with asthma susceptibility. However, their role in relation to asthma severity has not been delineated.ObjectiveWe hypothesized that circulating microRNAs could serve as biomarkers of changes in lung function in asthma patients.MethodsWe isolated microRNAs from serum samples obtained at randomization for 160 participants of the Childhood Asthma Management Program. Using a TaqMan microRNA array containing 754 microRNA primers, we tested for the presence of known asthma microRNAs, and assessed the association of the individual microRNAs with lung function as measured by FEV1/FVC, FEV1% and FVC%. We further tested the subset of FEV1/FVC microRNAs for sex-specific and lung developmental associations.ResultsOf the 108 well-detected circulating microRNAs, 74 (68.5%) had previously been linked to asthma susceptibility. We found 22 (20.3%), 4 (3.7%) and 8 (7.4%) microRNAs to be associated with FEV1/FVC, FEV1% and FVC%, respectively. 8 (of 22) FEV1/FVC, 3 (of 4) FEV1% and 1 (of 8) FVC% microRNAs had functionally validated target genes that have been linked via genome wide association studies to asthma and FEV1 change. Among the 22 FEV1/FVC microRNAs, 9 (40.9%) remain associated with FEV1/FVC in boys alone in a sex-stratified analysis (compared with 3 FEV1/FVC microRNAs in girls alone), 7 (31.8%) were associated with fetal lung development, and 3 (13.6%) in both. Ontology analyses revealed enrichment for pathways integral to asthma, including PPAR signaling, G-protein coupled signaling, actin and myosin binding, and respiratory system development.ConclusionsCirculating microRNAs reflect asthma biology and are associated with lung function differences in asthmatics. They may represent biomarkers of asthma severity.

The role of microRNAs in chronic respiratory disease: recent insights

“…This is in contrast to cell-based studies in which there was no differential expression of let-7 family members Polikepahad et al, 2010), though it may support the anti-inflammatory hypothesis for this miRNA (Kumar et al, 2011). miR-26a was also shown by Kho and colleagues to be differentially expressed in asthmatic serum and to correlate with lung function, as did several other miRNAs previously implicated in the disease, including miR-203 (Jardim et al, 2012;Solberg et al, 2012;Kho et al, 2016). In addition, miR-223, miR-142 and miR-629 levels in sputum were associated with asthma disease severity (Maes et al, 2016), and decreased miR-192 expression in peripheral blood mononuclear cells was observed 2 h following allergen challenge (Yamamoto et al, 2012).…”

Asthma diagnosis using integrated analysis of eosinophil microRNAs

“…In previous years, numerous studies have linked miRNAs to pulmonary diseases, such as asthma. These studies have been conducted in several cell types (eg, lymphocytes, airway epithelial and smooth muscle cells, and peripheral blood mononuclear cells) and in diverse biofluids, such as serum, bronchoalveolar lavage fluid, or exhaled breath condensate . However, no studies have been performed with eosinophil miRNAs in asthma context.…”

Identification of a plasma miRNA biomarker signature for allergic asthma: A translational approach

“…More recently, deregulation of miRNAs in airways has been shown in asthma—in both human and murine models . However, few studies have investigated circulating miRNAs as biomarkers in asthma . In contrast to cancer, where tumour‐specific miRNAs may be produced and released into body fluids in high levels by proliferating and lysing tumour cells, changes in the miRNA profile in asthma may be more subtle.…”