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MicroRNA profiling reveals a role for microRNA-218-5p in the pathogenesis of chronic obstructive pulmonary disease

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Abstract
RATIONALE: Since aberrant expression of microRNAs (miRNAs) can have a detrimental role in disease pathogenesis, we aimed to identify dysregulated miRNAs in lung tissue of patients with COPD. METHODS: We performed miRNA and mRNA profiling - using high throughput stem-loop RT-qPCR 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 microRNA-218-5p (miR-218-5p) was validated by RT-qPCR in an independent cohort of 71 patients, an in vivo murine model of COPD, and primary human bronchial epithelial cells (HBECs). 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 both smokers without airflow limitation and in patients with COPD, compared to never smokers. Decreased pulmonary expression of miR-218-5p was validated in an independent validation cohort, in cigarette smoke-exposed mice and in HBECs. 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.
Keywords
COPD, miR-218, lung, microRNA, chronic obstructive pulmonary disease, microRNA-218, CIGARETTE-SMOKE, GENE-EXPRESSION, COPD, LUNG, MICE, IDENTIFICATION, INFLAMMATION, GENOMICS, PATHWAY, SPUTUM

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MLA
Coninckx, Griet, Pieter Mestdagh, Francisco Avila Cobos, et al. “MicroRNA Profiling Reveals a Role for microRNA-218-5p in the Pathogenesis of Chronic Obstructive Pulmonary Disease.” AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE 195.1 (2017): 43–56. Print.
APA
Coninckx, G., Mestdagh, P., Avila Cobos, F., Verhamme, F., Maes, T., Vanaudenaerde, B. M., Seys, L., et al. (2017). MicroRNA profiling reveals a role for microRNA-218-5p in the pathogenesis of chronic obstructive pulmonary disease. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 195(1), 43–56.
Chicago author-date
Coninckx, Griet, Pieter Mestdagh, Francisco Avila Cobos, Fien Verhamme, Tania Maes, Bart M Vanaudenaerde, Leen Seys, et al. 2017. “MicroRNA Profiling Reveals a Role for microRNA-218-5p in the Pathogenesis of Chronic Obstructive Pulmonary Disease.” American Journal of Respiratory and Critical Care Medicine 195 (1): 43–56.
Chicago author-date (all authors)
Coninckx, Griet, Pieter Mestdagh, Francisco Avila Cobos, Fien Verhamme, Tania Maes, Bart M Vanaudenaerde, Leen Seys, Lies Lahousse, Richard Y Kim, Alan C Hsu, Peter A Wark, Philip M Hansbro, Guy Joos, Jo Vandesompele, Ken Bracke, and Guy Brusselle. 2017. “MicroRNA Profiling Reveals a Role for microRNA-218-5p in the Pathogenesis of Chronic Obstructive Pulmonary Disease.” American Journal of Respiratory and Critical Care Medicine 195 (1): 43–56.
Vancouver
1.
Coninckx G, Mestdagh P, Avila Cobos F, Verhamme F, Maes T, Vanaudenaerde BM, et al. MicroRNA profiling reveals a role for microRNA-218-5p in the pathogenesis of chronic obstructive pulmonary disease. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE. 2017;195(1):43–56.
IEEE
[1]
G. Coninckx et al., “MicroRNA profiling reveals a role for microRNA-218-5p in the pathogenesis of chronic obstructive pulmonary disease,” AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, vol. 195, no. 1, pp. 43–56, 2017.
@article{8137206,
  abstract     = {RATIONALE: Since aberrant expression of microRNAs (miRNAs) can have a detrimental role in disease pathogenesis, we aimed to identify dysregulated miRNAs in lung tissue of patients with COPD.
METHODS: We performed miRNA and mRNA profiling - using high throughput stem-loop RT-qPCR 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 microRNA-218-5p (miR-218-5p) was validated by RT-qPCR in an independent cohort of 71 patients, an in vivo murine model of COPD, and primary human bronchial epithelial cells (HBECs). 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 both smokers without airflow limitation and in patients with COPD, compared to never smokers. Decreased pulmonary expression of miR-218-5p was validated in an independent validation cohort, in cigarette smoke-exposed mice and in HBECs. 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.},
  author       = {Conickx, Griet and Mestdagh, Pieter and Avila Cobos, Francisco and Verhamme, Fien and Maes, Tania and Vanaudenaerde, Bart M and Seys, Leen and Lahousse, Lies and Kim, Richard Y and Hsu, Alan C and Wark, Peter A and Hansbro, Philip M and Joos, Guy and Vandesompele, Jo and Bracke, Ken and Brusselle, Guy},
  issn         = {1073-449X},
  journal      = {AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE},
  keywords     = {COPD,miR-218,lung,microRNA,chronic obstructive pulmonary disease,microRNA-218,CIGARETTE-SMOKE,GENE-EXPRESSION,COPD,LUNG,MICE,IDENTIFICATION,INFLAMMATION,GENOMICS,PATHWAY,SPUTUM},
  language     = {eng},
  number       = {1},
  pages        = {43--56},
  title        = {MicroRNA profiling reveals a role for microRNA-218-5p in the pathogenesis of chronic obstructive pulmonary disease},
  url          = {http://dx.doi.org/10.1164/rccm.201506-1182OC},
  volume       = {195},
  year         = {2017},
}

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