• Guoqing Wang, Rui Wang, Yael Strulovici-Barel, Jacqueline Salit, Michelle R Staudt, Joumana Ahmed, Ann E Tilley, Jenny Yee-Levin, Charleen Hollmann, Ben-Gary Harvey, Robert J Kaner, Jason G Mezey, Sriram Sridhar, Sreekumar G Pillai, Holly Hilton, Gerhard Wolff, Hans Bitter, Sudha Visvanathan, Jay S Fine, Christopher S Stevenson, and Ronald G Crystal.
• Department of Genetic Medicine, Weill Cornell Medical College, New York, New York, United States of America.
• Plos One. 2015 Jan 1; 10 (4): e0120824.

AbstractEven 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.

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