title: MicroRNAs as modulators of smoking-induced gene expression changes in human airway epithelium.
abstract: We have shown that smoking impacts bronchial airway gene expression and that heterogeneity in this response associates with smoking-related disease risk. In this study, we sought to determine whether microRNAs (miRNAs) play a role in regulating the airway gene expression response to smoking. We examined whole-genome miRNA and mRNA expression in bronchial airway epithelium from current and never smokers (n = 20) and found 28 miRNAs to be differentially expressed (P < 0.05) with the majority being down-regulated in smokers. We further identified a number of mRNAs whose expression level is highly inversely correlated with miRNA expression in vivo. Many of these mRNAs contain potential binding sites for the differentially expressed miRNAs in their 3'-untranslated region (UTR) and are themselves affected by smoking. We found that either increasing or decreasing the levels of mir-218 (a miRNA that is strongly affected by smoking) in both primary bronchial epithelial cells and H1299 cells was sufficient to cause a corresponding decrease or increase in the expression of predicted mir-218 mRNA targets, respectively. Further, mir-218 expression is reduced in primary bronchial epithelium exposed to cigarette smoke condensate (CSC), and alteration of mir-218 levels in these cells diminishes the induction of the predicted mir-218 target MAFG in response to CSC. These data indicate that mir-218 levels modulate the airway epithelial gene expression response to cigarette smoke and support a role for miRNAs in regulating host response to environmental toxins.
authors.affiliation: Pulmonary Center, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Schembri
authors.forename: Sriram
authors.initials: S
authors.lastname: Sridhar
authors.forename: Catalina
authors.initials: C
authors.lastname: Perdomo
authors.forename: Adam M
authors.initials: AM
authors.lastname: Gustafson
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Zhang
authors.forename: Ayla
authors.initials: A
authors.lastname: Ergun
authors.forename: Jining
authors.initials: J
authors.lastname: Lu
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Zhang
authors.forename: Jessica
authors.initials: J
authors.lastname: Bowers
authors.forename: Cyrus
authors.initials: C
authors.lastname: Vaziri
authors.forename: Kristen
authors.initials: K
authors.lastname: Ott
authors.forename: Kelly
authors.initials: K
authors.lastname: Sensinger
authors.forename: James J
authors.initials: JJ
authors.lastname: Collins
authors.forename: Jerome S
authors.initials: JS
authors.lastname: Brody
authors.forename: Robert
authors.initials: R
authors.lastname: Getts
authors.forename: Marc E
authors.initials: ME
authors.lastname: Lenburg
authors.forename: Avrum
authors.initials: A
authors.lastname: Spira
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D045744:Cell Line, Tumor; D004848:Epithelium / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D012306:Risk; D012907:Smoking; D014132:Trachea / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs