Micrornas As Modulators of Smoking-Induced Gene Expression Changes in Human Airway Epithelium
MicroRNAs as modulators of smoking-induced gene expression changes in human airway epithelium Frank Schembria,1, Sriram Sridharb,1, Catalina Perdomoc, Adam M. Gustafsond, Xiaoling Zhangd, Ayla Ergune, Jining Lua, Gang Liua, Xiaohui Zhanga, Jessica Bowersf, Cyrus Vazirib, Kristen Ottc, Kelly Sensingerf, James J. Collinse, Jerome S. Brodya, Robert Gettsf, Marc E. Lenburga,b,d, and Avrum Spiraa,b,d,2 aPulmonary Center, bDepartment of Pathology and Laboratory Medicine, and cGenetics and Genomics Graduate Program, Boston University School of Medicine, Boston, MA 02118; dBioinformatics Program, Boston University School of Engineering, Boston, MA 02215; eDepartment of Biomedical Engineering and Center for BioDynamics and Howard Hughes Medical Institute, Boston University, Boston, MA 02215; and fGenisphere, Inc., Hatfield, PA 19440 Edited by Charles R. Cantor, Sequenom Inc., San Diego, CA, and approved November 21, 2008 (received for review July 3, 2008) We have shown that smoking impacts bronchial airway gene Hundreds of human miRNAs have been cloned (11), with each of expression and that heterogeneity in this response associates with them predicted to regulate hundreds of genes by complementary smoking-related disease risk. In this study, we sought to determine binding to the 3Ј-untranslated region (UTR) of target mRNAs (12). whether microRNAs (miRNAs) play a role in regulating the airway A number of miRNAs have been shown to play important roles in gene expression response to smoking. We examined whole-ge- developmental timing, cell death, carcinogenesis, and stress responses in nome miRNA and mRNA expression in bronchial airway epithelium vitro (13–16), such as hypoxia (17). Whereas miRNA expression has and found 28 miRNAs to been examined in lung tumors (18–24), neither the expression of (20 ؍ from current and never smokers (n be differentially expressed (P < 0.05) with the majority being miRNA in bronchial epithelium nor the effect of smoking on bronchial down-regulated in smokers.
[Show full text]