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Chronic obstructive pulmonary disease
Original article
Gene expression networks in COPD: microRNA and mRNA regulation
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  1. Michael E Ezzie1,
  2. Melissa Crawford1,
  3. Ji-Hoon Cho2,
  4. Robert Orellana1,
  5. Shile Zhang2,
  6. Richard Gelinas2,
  7. Kara Batte1,
  8. Lianbo Yu1,
  9. Gerard Nuovo1,
  10. David Galas2,
  11. Philip Diaz1,
  12. Kai Wang2,
  13. S Patrick Nana-Sinkam1
  1. 1Department of Medicine, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Medical Center, Columbus, Ohio, USA
  2. 2Institute for Systems Biology, Seattle, Washington, USA
  1. Correspondence to Dr S Patrick Nana-Sinkam, Ohio State University Medical Center, Davis HLRI, 473 W 12th Ave, Room 201, Columbus, OH 43210, USA; patrick.nana-sinkam{at}osumc.edu

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.

  • Chronic obstructive pulmonary disease
  • emphysema
  • microRNA
  • gene expression
  • COPD mechanismsCOPD exacerbations
  • COPD exacerbations
  • COPD pathology
  • COPD pharmacology
  • emphysema
  • lung volume reduction surgery
  • pulmonary rehabilitation
  • tobacco and the lung
  • interstitial fibrosis
  • COPD epidemiology
  • lung cancer
  • airway epithelium

https://doi.org/10.1136/thoraxjnl-2011-200089

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    Footnotes

    • ME and MC contributed equally to this manuscript.

    • Funding This work was supported by NIH grant R03 HL095425 (SNS) and by the Flight Attendant Medical Research Institute (FAMRI) (MEE), Pulmonary Systems Biology Initiative of the Battelle Memorial Institute (KW, SZ, RG) as well as support from the University of Luxembourg and the Luxembourg Centre for Systems Biomedicine (DG, KW, JHC, RG).

    • Competing interests None.

    • Ethics approval This study was approved by IRB Ohio State University.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data sharing statement All data generated will be uploaded to the appropriate online genomic data banks.