A-to-I editing of miR-200b-3p in airway cells is associated with moderate-to-severe asthma.

Background Asthma is a chronic lung disease characterised by persistent airway inflammation. Altered microRNA-mediated gene silencing in bronchial epithelial cells has been reported in asthma, yet ADAR-mediated microRNA editing in asthma remains unexplored. Methods We first identified A-to-I edited sites in microRNAs in bronchial epithelial cells from 142 adult asthma cases and controls. A-to-I edited sites were tested for associations with asthma severity and clinical measures of asthma. Paired RNA-seq data was used to perform pathway enrichments and test for associations with bioinformatically predicted target genes of the unedited and edited microRNAs. Results Of 19 A-to-I edited sites detected in these microRNAs, one site at position 5 of miR-200b-3p was edited less frequently in cases compared to controls (p=0.013), and especially compared to cases with moderate (p=0.029) and severe (p=3.9×10−4), but not mild (p=0.38), asthma. Bioinformatic prediction revealed 232 target genes of the edited miR-200b-3p, which were enriched for both IL-4 and interferon gamma signalling pathways and included the SOCS1 (suppressor of cytokine signalling 1) gene. SOCS1 was more highly expressed in moderate (p=0.017) and severe (p=5.4×10−3) asthma cases compared to controls. Moreover, both miR-200b-3p editing and SOCS1 were associated with BAL eosinophil levels. Conclusion Reduced A-to-I editing of the 5th position of miR-200b-3p in lower airway cells from moderate-to-severe asthmatics may lead to overexpression of SOCS1 and impaired cytokine signalling. We proposed ADAR-mediated editing as an epigenetic mechanism contributing to features of moderate-to-severe asthma in adulthood.