title: Gene expression networks in COPD: microRNA and mRNA regulation.
abstract: BACKGROUND
  The mechanisms underlying chronic obstructive pulmonary disease (COPD) remain unclear. MicroRNAs (miRNAs or miRs) are small non-coding RNA molecules that modulate the levels of specific genes and proteins. Identifying expression patterns of miRNAs in COPD may enhance our understanding of the mechanisms of disease. A study was undertaken to determine if miRNAs are differentially expressed in the lungs of smokers with and without COPD. miRNA and mRNA expression were compared to enrich for biological networks relevant to the pathogenesis of COPD.
  
  
  METHODS
  Lung tissue from smokers with no evidence of obstructive lung disease (n=9) and smokers with COPD (n=26) was examined for miRNA and mRNA expression followed by validation. We then examined both miRNA and mRNA expression to enrich for relevant biological pathways.
  
  
  RESULTS
  70 miRNAs and 2667 mRNAs were differentially expressed between lung tissue from subjects with COPD and smokers without COPD. miRNA and mRNA expression profiles enriched for biological pathways that may be relevant to the pathogenesis of COPD including the transforming growth factor β, Wnt and focal adhesion pathways. miR-223 and miR-1274a were the most affected miRNAs in subjects with COPD compared with smokers without obstruction. miR-15b was increased in COPD samples compared with smokers without obstruction and localised to both areas of emphysema and fibrosis. miR-15b was differentially expressed within GOLD classes of COPD. Expression of SMAD7, which was validated as a target for miR-15b, was decreased in bronchial epithelial cells in COPD.
  
  
  CONCLUSIONS
  miRNA and mRNA are differentially expressed in individuals with COPD compared with smokers without obstruction. Investigating these relationships may further our understanding of the mechanisms of disease.
authors.affiliation: Department of Medicine, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Medical Center, Columbus, Ohio 43210, USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Ezzie
authors.forename: Melissa
authors.initials: M
authors.lastname: Crawford
authors.forename: Ji-Hoon
authors.initials: JH
authors.lastname: Cho
authors.forename: Robert
authors.initials: R
authors.lastname: Orellana
authors.forename: Shile
authors.initials: S
authors.lastname: Zhang
authors.forename: Richard
authors.initials: R
authors.lastname: Gelinas
authors.forename: Kara
authors.initials: K
authors.lastname: Batte
authors.forename: Lianbo
authors.initials: L
authors.lastname: Yu
authors.forename: Gerard
authors.initials: G
authors.lastname: Nuovo
authors.forename: David
authors.initials: D
authors.lastname: Galas
authors.forename: Philip
authors.initials: P
authors.lastname: Diaz
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.forename: S Patrick
authors.initials: SP
authors.lastname: Nana-Sinkam
mesh_terms: D000368:Aged; D001980:Bronchi / Q000378:metabolism; D016000:Cluster Analysis; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000235:genetics*; D053263:Gene Regulatory Networks / Q000235:genetics*; D006801:Humans; D008168:Lung / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D051906:Smad7 Protein / Q000096:biosynthesis / Q000235:genetics; D012907:Smoking / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics; D060449:Wnt Signaling Pathway / Q000235:genetics
chemical_list: C505361:MIRN15 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; C497806:SMAD7 protein, human; D051906:Smad7 Protein; D016212:Transforming Growth Factor beta