TY - JOUR T1 - LSC Abstract – microRNA profiling reveals a role for microRNA-218-5p in the pathogenesis of chronic obstructive pulmonary disease JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.congress-2016.PA4025 VL - 48 IS - suppl 60 SP - PA4025 AU - Griet Conickx AU - Pieter Mestdagh AU - Francisco Avila Cobos AU - Fien Verhamme AU - Tania Maes AU - Bart Vanaudenaerde AU - Lies Lahousse AU - Guy Joos AU - Jo Vandesompele AU - Ken Bracke AU - Guy Brusselle Y1 - 2016/09/01 UR - http://erj.ersjournals.com/content/48/suppl_60/PA4025.abstract N2 - Rationale: Since aberrant expression of microRNAs (miRNAs) has been implicated in disease pathogenesis, we aimed to identify dysregulated miRNAs in lungs of patients with COPD.Methods: We performed miRNA and mRNA profiling on lung tissue of a screening cohort (n=30) encompassing never smokers, smokers without airflow limitation and smokers with COPD. Differential expression of microRNA-218-5p (miR-218-5p) was validated by RT-qPCR in an independent cohort (n=71). Localization of miR-218-5p was assessed by in situ hybridization. Perturbation of miR-218-5p was obtained by transfecting primary normal human bronchial epithelial (NHBE) cells with a miR-218-5p inhibitor or mimic, followed by polyA-sequencing and RT-qPCR for target genes and markers of inflammation.Results: Several miRNAs were differentially expressed among the different patient groups. Interestingly, miR-218-5p was significantly down-regulated in smokers without airflow limitation and in patients with COPD, compared to never smokers. Decreased pulmonary expression of miR-218-5p was confirmed in an independent validation cohort. Importantly, expression of miR-218-5p strongly correlated with airflow limitation (FEV1, FEV1/FVC) and lung diffusion (DLCO, KCO). Cellular localization of miR-218-5p revealed highest expression of miR-218-5p in bronchial airway epithelium. Additionally, in vitro perturbation of miR-218-5p in NHBE cells together with gene set enrichment analysis suggest an involvement of miR-218-5p in inflammatory and immune responses.Conclusions: These translational research findings highlight a potential role for miR-218-5p in the pathogenesis of COPD.This abstract has been presented previously at the European Respiratory Society's Lung Science Conference in March 2016. ER -