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

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. StevensonRonald Crystal

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37 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere0120824
JournalPLoS One
Volume10
Issue number4
DOIs
Publication statusPublished - 17 Apr 2015
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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    Wang, G., Wang, R., Strulovici-Barel, Y., Salit, J., Staudt, M. R., Ahmed, J., Tilley, A. E., Yee-Levin, J., Hollmann, C., Harvey, B. G., Kaner, R. J., Mezey, J. G., Sridhar, S., Pillai, S. G., Hilton, H., Wolff, G., Bitter, H., Visvanathan, S., Fine, J. S., ... Crystal, R. (2015). Persistence of smoking-induced dysregulation of MiRNA expression in the small airway epithelium despite smoking cessation. PLoS One, 10(4), [e0120824]. https://doi.org/10.1371/journal.pone.0120824