Regulation of CBL and ESR1 expression by microRNA-22-3p 513a-5p and 625-5p may impact the pathogenesis of dust mite-induced pediatric asthma

摘要

Despite evidence for the involvement of microRNAs (miRNAs or miRs) in pediatric asthma, the mechanism responsible has not yet been fully elucidated. We aimed to identify novel miRNAs and to study their pathogenic role(s) in children with dust mite-induced asthma in order to gain a better understanding of the underlying mechanism responsible for this disease. For this purpose, 62 patients with asthma as well as 62 age- and gender-matched healthy controls were recruited. Twelve pairs of subjects were randomly subjected to microarray-based discovery analysis using a miRCURY LNA™ array. The differential expression of miRNAs and their targeted messenger RNAs were validated using RT-qPCR. Plasma concentrations of cytokines were determined using an enzyme-linked immunosorbent assay (ELISA) kit. The results revealed that three novel miRNAs - miR-22-3p, miR-513a-5p and miR-625-5p - were significantly downregulated in the asthma group compared with the control group (p<0.01), whereas the transcript levels of Cbl proto-oncogene, E3 ubiquitin protein ligase (CBL), peroxisome proliferator-activated receptor gamma, coactivator 1 beta (PPARGC1B), and estrogen receptor 1 (ESR1) that are targeted by these miRNAs were increased (p<0.01). There were significant differences in the plasma concentrations of γ-interferon, tumor necrosis factor-α, interleukin (IL)-12 and IL-10 between the two groups (p<0.05). Thus, miR-513a-5p, miR-22-3p and miR-625-5p may have an impact on the regulation of the immune response and inflammatory cytokine pathways through the regulation of their target gene(s), CBL, PPARGC1B and ESR1, which may then lead to a dust mite-induced asthma attack. Our findings may provide novel insights into the pathogenesis of pediatric asthma.