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MicroRNA expression in induced sputum of smokers and patients with chronic obstructive pulmonary disease

Geert Van Pottelberge, Pieter Mestdagh UGent, Ken Bracke UGent, Olivier Thas UGent, YANNICK VAN DURME UGent, Guy Joos UGent, Jo Vandesompele UGent and Guy Brusselle UGent (2011) AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE. 183(7). p.898-906
abstract
Rationale: Chronic obstructive pulmonary disease (COPD) is characterized by progressive inflammation in the airways and lungs combined with disturbed homeostatic functions of pulmonary cells. MicroRNAs (miRNAs) have the ability to regulate these processes by interfering with gene transcription and translation. Objectives: We aimed to identify miRNA expression in induced sputum and examined whether the expression of miRNAs differed between patients with COPD and subjects without airflow limitation. Methods: Expression of 627 miRNAs was evaluated in induced sputum supernatant of 32 subjects by stem loop reverse transcription-quantitative polymerase chain reaction. Differentially expressed miRNAs were validated in an independent replication cohort of 41 subjects. Enrichment of miRNA target genes was identified by in silico analysis. Protein expression of target genes was determined by ELISA. Measurements and Main Results: Thirty-four miRNAs were differentially expressed between never-smokers and current smokers without airflow limitation in the screening cohort. Eight miRNAs were expressed at a significantly lower level in current-smoking patients with COPD compared with never-smokers without airflow limitation. Reduced expression of let-7c and miR-125b in patients with COPD compared with healthy subjects was confirmed in the validation cohort. Target genes of let-7c were significantly enriched in the sputum of patients with severe COPD. The concentration of tumor necrosis factor receptor type II (TNFR-II, implicated in COPD pathogenesis and a predicted target gene of let-7c) was inversely correlated with the sputum levels of let-7c. Conclusions: let-7c is significantly reduced in the sputum of currently smoking patients with COPD and is associated with increased expression of TNFR-II.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
chronic obstructive pulmonary disease, sputum, microRNA, smoking, let-7c, CIGARETTE-SMOKE, AIRWAY INFLAMMATION, LUNG, EMPHYSEMA, COPD, FIBROSIS, BURDEN, ASTHMA, CANCER
journal title
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
Am. J. Respir. Crit. Care Med.
volume
183
issue
7
pages
898 - 906
Web of Science type
Article
Web of Science id
000289318800016
JCR category
RESPIRATORY SYSTEM
JCR impact factor
11.08 (2011)
JCR rank
1/48 (2011)
JCR quartile
1 (2011)
ISSN
1073-449X
DOI
10.1164/rccm.201002-0304OC
project
Bioinformatics: from nucleotids to networks (N2N)
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
1259597
handle
http://hdl.handle.net/1854/LU-1259597
date created
2011-06-10 11:08:07
date last changed
2016-12-19 15:42:48
@article{1259597,
  abstract     = {Rationale: Chronic obstructive pulmonary disease (COPD) is characterized by progressive inflammation in the airways and lungs combined with disturbed homeostatic functions of pulmonary cells. MicroRNAs (miRNAs) have the ability to regulate these processes by interfering with gene transcription and translation.
Objectives: We aimed to identify miRNA expression in induced sputum and examined whether the expression of miRNAs differed between patients with COPD and subjects without airflow limitation.
Methods: Expression of 627 miRNAs was evaluated in induced sputum supernatant of 32 subjects by stem loop reverse transcription-quantitative polymerase chain reaction. Differentially expressed miRNAs were validated in an independent replication cohort of 41 subjects. Enrichment of miRNA target genes was identified by in silico analysis. Protein expression of target genes was determined by ELISA.
Measurements and Main Results: Thirty-four miRNAs were differentially expressed between never-smokers and current smokers without airflow limitation in the screening cohort. Eight miRNAs were expressed at a significantly lower level in current-smoking patients with COPD compared with never-smokers without airflow limitation. Reduced expression of let-7c and miR-125b in patients with COPD compared with healthy subjects was confirmed in the validation cohort. Target genes of let-7c were significantly enriched in the sputum of patients with severe COPD. The concentration of tumor necrosis factor receptor type II (TNFR-II, implicated in COPD pathogenesis and a predicted target gene of let-7c) was inversely correlated with the sputum levels of let-7c.
Conclusions: let-7c is significantly reduced in the sputum of currently smoking patients with COPD and is associated with increased expression of TNFR-II.},
  author       = {Van Pottelberge, Geert and Mestdagh, Pieter and Bracke, Ken and Thas, Olivier and VAN DURME, YANNICK and Joos, Guy and Vandesompele, Jo and Brusselle, Guy},
  issn         = {1073-449X},
  journal      = {AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE},
  keyword      = {chronic obstructive pulmonary disease,sputum,microRNA,smoking,let-7c,CIGARETTE-SMOKE,AIRWAY INFLAMMATION,LUNG,EMPHYSEMA,COPD,FIBROSIS,BURDEN,ASTHMA,CANCER},
  language     = {eng},
  number       = {7},
  pages        = {898--906},
  title        = {MicroRNA expression in induced sputum of smokers and patients with chronic obstructive pulmonary disease},
  url          = {http://dx.doi.org/10.1164/rccm.201002-0304OC},
  volume       = {183},
  year         = {2011},
}

Chicago
Van Pottelberge, Geert, Pieter Mestdagh, Ken Bracke, Olivier Thas, YANNICK VAN DURME, Guy Joos, Jo Vandesompele, and Guy Brusselle. 2011. “MicroRNA Expression in Induced Sputum of Smokers and Patients with Chronic Obstructive Pulmonary Disease.” American Journal of Respiratory and Critical Care Medicine 183 (7): 898–906.
APA
Van Pottelberge, G., Mestdagh, P., Bracke, K., Thas, O., VAN DURME, Y., Joos, G., Vandesompele, J., et al. (2011). MicroRNA expression in induced sputum of smokers and patients with chronic obstructive pulmonary disease. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 183(7), 898–906.
Vancouver
1.
Van Pottelberge G, Mestdagh P, Bracke K, Thas O, VAN DURME Y, Joos G, et al. MicroRNA expression in induced sputum of smokers and patients with chronic obstructive pulmonary disease. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE. 2011;183(7):898–906.
MLA
Van Pottelberge, Geert, Pieter Mestdagh, Ken Bracke, et al. “MicroRNA Expression in Induced Sputum of Smokers and Patients with Chronic Obstructive Pulmonary Disease.” AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE 183.7 (2011): 898–906. Print.