Persistence of smoking-induced dysregulation of miRNA expression in the small airway epithelium despite smoking cessation.

Publication TypeJournal Article
Year of Publication2015
AuthorsWang G, Wang R, Strulovici-Barel Y, Salit J, Staudt MR, Ahmed J, Tilley AE, Yee-Levin J, Hollmann C, Harvey B-G, Kaner RJ, Mezey JG, Sridhar S, Pillai SG, Hilton H, Wolff G, Bitter H, Visvanathan S, Fine JS, Stevenson CS, Crystal RG
JournalPLoS One
Date Published2015
KeywordsAdult, Bronchoscopy, Cell Differentiation, Cluster Analysis, Cotinine, Down-Regulation, Epithelium, Female, Humans, Male, MicroRNAs, Middle Aged, Nicotine, Respiratory Mucosa, Smoking, Smoking Cessation, Up-Regulation, Wnt Signaling Pathway

Even after quitting smoking, the risk of the development of chronic obstructive pulmonary disease (COPD) and lung cancer remains significantly higher compared to healthy nonsmokers. Based on the knowledge that COPD and most lung cancers start in the small airway epithelium (SAE), we hypothesized that smoking modulates miRNA expression in the SAE linked to the pathogenesis of smoking-induced airway disease, and that some of these changes persist after smoking cessation. SAE was collected from 10th to 12th order bronchi using fiberoptic bronchoscopy. Affymetrix miRNA 2.0 arrays were used to assess miRNA expression in the SAE from 9 healthy nonsmokers and 10 healthy smokers, before and after they quit smoking for 3 months. Smoking status was determined by urine nicotine and cotinine measurement. There were significant differences in the expression of 34 miRNAs between healthy smokers and healthy nonsmokers (p<0.01, fold-change >1.5), with functions associated with lung development, airway epithelium differentiation, inflammation and cancer. After quitting smoking for 3 months, 12 out of the 34 miRNAs did not return to normal levels, with Wnt/β-catenin signaling pathway being the top identified enriched pathway of the target genes of the persistent dysregulated miRNAs. In the context that many of these persistent smoking-dependent miRNAs are associated with differentiation, inflammatory diseases or lung cancer, it is likely that persistent smoking-related changes in SAE miRNAs play a role in the subsequent development of these disorders.

Alternate JournalPLoS ONE
PubMed ID25886353
PubMed Central IDPMC4401720
Grant ListP20 HL113443 / HL / NHLBI NIH HHS / United States
1K23 HL103837 / HL / NHLBI NIH HHS / United States
P50 HL084936 / HL / NHLBI NIH HHS / United States
UL1-RR024143 / RR / NCRR NIH HHS / United States
UL1-RR024996 / RR / NCRR NIH HHS / United States
1R01HL107882 / HL / NHLBI NIH HHS / United States
UL1 TR000457 / TR / NCATS NIH HHS / United States