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Molecular & Cellular Toxicology

, Volume 13, Issue 2, pp 207–212 | Cite as

Altered miRNA expression in lung tissues of patients with chronic obstructive pulmonary disease

  • Woo Jin Kim
  • Jae Hyun Lim
  • Yoonki Hong
  • Seok-Ho Hong
  • Chi Young Bang
  • Jae Seung Lee
  • Yeon-Mok Oh
  • Ju Han KimEmail author
Original Paper

Abstract

Chronic obstructive pulmonary disease (COPD) is a complex disorder characterized by airflow limitation. Epigenetic control affects gene expression in the lung, and microRNAs (miRNAs) are one of the primary types of epigenetic modifiers. In this study, lung tissues were obtained from 15 COPD patients and 11 subjects with normal lung function. RNA was isolated from the samples, and small RNA sequencing was performed and miRNAs that were differentially expressed between the COPD and control lungs were identified. A total of 12 miRNAs were shown to be differentially expressed (false discovery rate (FDR)<0.05) between the lung tissues of COPD and control subjects. Based on the predicted target mRNAs of differentially expressed miRNAs, the gene ontologies that were most enriched were nuclear lumen and transcription initiation. Further investigation of these miRNAs and their target genes will enhance our understanding of the molecular mechanisms involved in COPD.

Keywords

Chronic obstructive pulmonary disease microRNA Sequencing 

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References

  1. 1.
    Vestbo, J. et al. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease: GOLD Executive Summary. Am J Respir Crit Care Med 187:347–365 (2013).CrossRefPubMedGoogle Scholar
  2. 2.
    Sun, K. & Lai, E. C. Adult-specific functions of animal microRNAs. Nat Rev Genet 14:535–548 (2013).CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Rupani, H., Sanchez-Elsner, T. & Howarth, P. MicroRNAs and respiratory diseases. Eur Respir J 41:695–705 (2013).CrossRefPubMedGoogle Scholar
  4. 4.
    Perdomo, C., Spira, A. & Schembri, F. MiRNAs as regulators of the response to inhaled environmental toxins and airway carcinogenesis. Mutat Res 717:32–37 (2011).CrossRefPubMedGoogle Scholar
  5. 5.
    Rebane, A. & Akdis, C. A. MicroRNAs: Essential players in the regulation of inflammation. J Allergy Clin Immunol 132:15–26 (2013).CrossRefPubMedGoogle Scholar
  6. 6.
    Booton, R. & Lindsay, M. A. EMerging role of micrornas and long noncoding rnas in respiratory disease. Chest 146:193–204 (2014).CrossRefPubMedGoogle Scholar
  7. 7.
    Ezzie, M. E. et al. Gene expression networks in COPD: microRNA and mRNA regulation. Thorax 67:122–131 (2012).CrossRefPubMedGoogle Scholar
  8. 8.
    Pottelberge, G. R. V. et al. MicroRNA Expression in Induced Sputum of Smokers and Patients with Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med 183:898–906 (2011).CrossRefPubMedGoogle Scholar
  9. 9.
    Schembri, F. et al. MicroRNAs as modulators of smoking-induced gene expression changes in human airway epithelium. Proc Natl Acad Sci 106:2319–2324 (2009).CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Molina-Pinelo, S. et al. MicroRNA clusters: dysregulation in lung adenocarcinoma and COPD. Eur Respir J 43:1740–1749 (2014).CrossRefPubMedGoogle Scholar
  11. 11.
    Leidinger, P. et al. Specific peripheral miRNA profiles for distinguishing lung cancer from COPD. Lung Cancer 74:41–47 (2011).CrossRefPubMedGoogle Scholar
  12. 12.
    Fan, J.-B., Gunaratne, P., Coarfa, C., Soibam, B. & Tandon, A. in Next-Generation MicroRNA Expression Profiling Technology Vol. 822 Methods in Molecular Biology 273–288 (Humana Press, 2012).Google Scholar
  13. 13.
    De Smet, E. G., Mestdagh, P., Vandesompele, J., Brusselle, G. G. & Bracke, K. R. Non-coding RNAs in the pathogenesis of COPD. Thorax 70:782–791 (2015).CrossRefPubMedGoogle Scholar
  14. 14.
    Graff, J. W. et al. Cigarette Smoking Decreases Global MicroRNA Expression in Human Alveolar Macrophages. PLoS ONE 7:e44066 (2012).CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Akbas, F., Coskunpinar, E., Aynacı, E., Müsteri Oltulu, Y. & Yildiz, P. Analysis of serum micro-RNAs as potential biomarker in chronic obstructive pulmonary disease. Exp Lung Res 38:286–294 (2012).CrossRefPubMedGoogle Scholar
  16. 16.
    Zhou, X. et al. MiR-28-3p as a potential plasma marker in diagnosis of pulmonary embolism. Thrombosis Res 138:91–95 (2016).CrossRefGoogle Scholar
  17. 17.
    Christenson, S. et al. miR-638 regulates gene expression networks associated with emphysematous lung destruction. Genome Med 5:114 (2013).CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Belkaya, S. & van Oers, N. S. C. Transgenic Expression of MicroRNA-181d Augments the Stress-Sensitivity of CD4+CD8+ Thymocytes. PLoS ONE 9:e85274 (2014).CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Savarimuthu Francis, S. et al. MicroRNA-34c is associated with emphysema severity and modulates SERPINE1 expression. BMC Genomics 15:88 (2014).CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Mathew, L. K. et al. Restricted Expression of miR-30c-2-3p and miR-30a-3p in Clear Cell Renal Cell Carcinomas Enhances HIF2α Activity. Cancer Discov 4:53–60 (2014).CrossRefPubMedGoogle Scholar
  21. 21.
    Deng, L. et al. MicroRNA-143 Activation Regulates Smooth Muscle and Endothelial Cell Crosstalk in Pulmonary Arterial Hypertension. Circulation Res 117:870–883 (2015).CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Incoronato, M. et al. miR-212 Increases Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Sensitivity in Non-Small Cell Lung Cancer by Targeting the Antiapoptotic Protein PED. Cancer Res 70:3638–3646 (2010).CrossRefPubMedGoogle Scholar
  23. 23.
    Hassan, T. et al. miR-199a-5p Silencing Regulates the Unfolded Protein Response in Chronic Obstructive Pulmonary Disease and α1-Antitrypsin Deficiency. Am J Respir Crit Care Med 189:263–273 (2014).CrossRefPubMedGoogle Scholar
  24. 24.
    Chatila, W. M. et al. Blunted expression of miR-199a-5p in regulatory T cells of patients with chronic obstructive pulmonary disease compared to unaffected smokers. Clin Exp Immunol 177:341–352 (2014).CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Gross, T. J. et al. A MicroRNA Processing Defect in Smokers’ Macrophages Is Linked to SUMOylation of the Endonuclease DICER. J Biol Chem 289:12823–12834 (2014).CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Lee, J.-H. & Skalnik, D. G. Wdr82 Is a C-Terminal Domain-Binding Protein That Recruits the Setd1A Histone H3-Lys4 Methyltransferase Complex to Transcription Start Sites of Transcribed Human Genes. Mol Cell Biol 28:609–618 (2008).CrossRefPubMedGoogle Scholar
  27. 27.
    Bi, Y. et al. WDR82, a Key Epigenetics-Related Factor, Plays a Crucial Role in Normal Early Embryonic Development in Mice. Biol Reprod 84:756–764 (2011).CrossRefPubMedGoogle Scholar
  28. 28.
    Schamberger, A. C., Mise, N., Meiners, S. & Eickelberg, O. Epigenetic mechanisms in COPD: implications for pathogenesis and drug discovery. Expert Opin Drug Discov 9:609–628 (2014).CrossRefPubMedGoogle Scholar
  29. 29.
    Miller, M. R. et al. Standardisation of spirometry. Eur Respir J 26:319–338 (2005).CrossRefPubMedGoogle Scholar
  30. 30.
    Wang, W.-C. et al. miRExpress: Analyzing highthroughput sequencing data for profiling microRNA expression. BMC Bioinformatics 10:328 (2009).CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Kim, W. J. et al. Comprehensive Analysis of Transcriptome Sequencing Data in the Lung Tissues of COPD Subjects. Int J Genomics 2015:9 (2015).Google Scholar
  32. 32.
    Hsu, S.-D. et al. miRTarBase: a database curates experimentally validated microRNA-target interactions. Nucleic Acids Res 39:D163–D169 (2011).CrossRefPubMedGoogle Scholar

Copyright information

© The Korean Society of Toxicogenomics and Toxicoproteomics and Springer Science+Business Media B.V. 2017

Authors and Affiliations

  • Woo Jin Kim
    • 1
  • Jae Hyun Lim
    • 2
  • Yoonki Hong
    • 1
  • Seok-Ho Hong
    • 1
  • Chi Young Bang
    • 1
  • Jae Seung Lee
    • 3
  • Yeon-Mok Oh
    • 3
  • Ju Han Kim
    • 2
    Email author
  1. 1.Department of Internal Medicine and Environmental Health Center, Kangwon National University Hospital, School of MedicineKangwon National UniversityChuncheonRepublic of Korea
  2. 2.Seoul National University Biomedical Informatics and Systems Biomedical Informatics Research Center, Division of Biomedical InformaticsSeoul National University College of MedicineSeoulRepublic of Korea
  3. 3.Department of Pulmonary and Critical Care Medicine, and Clinical Research Center for Chronic Obstructive Airway Diseases, Asan Medical CenterUniversity of Ulsan College of MedicineSeoulRepublic of Korea

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