- Title
- MicroRNA profiling reveals a role for microRNA-218-5p in the pathogenesis of chronic obstructive pulmonary disease
- Creator
- Conickx, Griet; Mestdagh, Pieter; Wark, Peter A.; Hansbro, Philip M.; Joos, Guy F.; Vandesompele, Jo; Bracke, Ken R.; Brusselle, Guy G.; Cobos, Francisco Avila; Verhamme, Fien M.; Maes, Tania; Vanaudenaerde, Bart M.; Seys, Leen J. M.; Lahousse, Lies; Kim, Richard Y.; Hsu, Alan C.
- Relation
- American Journal of Respiratory and Critical Care Medicine Vol. 195, Issue 1, p. 43-56
- Publisher Link
- http://dx.doi.org/10.1164/rccm.201506-1182OC
- Publisher
- American Thoracic Society
- Resource Type
- journal article
- Date
- 2017
- Description
- Rationale: Aberrant expression of microRNAs (miRNAs) can have a detrimental role in disease pathogenesis. Objectives: To identify dysregulated miRNAs in lung tissue of patients with chronic obstructive pulmonary disease (COPD). Methods: We performed miRNA and mRNA profiling using high throughput stem-loop reverse-transcriptase quantitative polymerase chain reaction and mRNA microarray, respectively, on lung tissue of 30 patients (screening cohort) encompassing 8 never-smokers, 10 smokers without airflow limitation, and 12 smokers with COPD. Differential expression of miRNA-218-5p (miR-218-5p) was validated by reverse-transcriptase quantitative polymerase chain reaction in an independent cohort of 71 patients, an in vivo murine model of COPD, and primary human bronchial epithelial cells. Localization of miR-218-5p was assessed by in situ hybridization. In vitro and in vivo perturbation of miR-218-5p combined with RNA sequencing and gene set enrichment analysis was used to elucidate its functional role in COPD pathogenesis. Measurements and Main 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 with never-smokers. Decreased pulmonary expression of miR-218-5p was validated in an independent validation cohort, in cigarette smoke-exposed mice, and in human bronchial epithelial cells. Importantly, expression of miR-218-5p strongly correlated with airway obstruction. Furthermore, cellular localization of miR-218-5p in human and murine lung revealed highest expression of miR-218-5p in the bronchial airway epithelium. Perturbation experiments with a miR-218-5p mimic or inhibitor demonstrated a protective role of miR-218-5p in cigarette smoke-induced inflammation and COPD. Conclusions: We highlight a role for miR-218-5p in the pathogenesis of COPD.
- Subject
- microRNA; lung; chronic obstructive pulmonary disease; microRNA-218
- Identifier
- http://hdl.handle.net/1959.13/1391107
- Identifier
- uon:33159
- Identifier
- ISSN:1073-449X
- Language
- eng
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