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.
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.
Authors: Rebecca L Kusko; John F Brothers; John Tedrow; Kusum Pandit; Luai Huleihel; Catalina Perdomo; Gang Liu; Brenda Juan-Guardela; Daniel Kass; Sherry Zhang; Marc Lenburg; Fernando Martinez; John Quackenbush; Frank Sciurba; Andrew Limper; Mark Geraci; Ivana Yang; David A Schwartz; Jennifer Beane; Avrum Spira; Naftali Kaminski Journal: Am J Respir Crit Care Med Date: 2016-10-15 Impact factor: 21.405
Authors: Roland Hubaux; Daiana D Becker-Santos; Katey S S Enfield; Stephen Lam; Wan L Lam; Victor D Martinez Journal: Metabolomics (Los Angel) Date: 2012-03-21
Authors: Thomas J Gross; Linda S Powers; Ryan L Boudreau; Brandi Brink; Anna Reisetter; Khushboo Goel; Alicia K Gerke; Ihab H Hassan; Martha M Monick Journal: J Biol Chem Date: 2014-03-25 Impact factor: 5.157
Authors: Rebecca C Fry; Julia E Rager; Rebecca Bauer; Elizabeth Sebastian; David B Peden; Ilona Jaspers; Neil E Alexis Journal: Am J Physiol Lung Cell Mol Physiol Date: 2014-04-25 Impact factor: 5.464