Inflammation Research

, Volume 64, Issue 2, pp 119–126 | Cite as

Microarray analysis of long non-coding RNAs in COPD lung tissue

  • Hui Bi
  • Ji Zhou
  • Dandan Wu
  • Wei Gao
  • Lingling Li
  • Like Yu
  • Feng Liu
  • Mao Huang
  • Ian M. Adcock
  • Peter J. Barnes
  • Xin YaoEmail author
Original Research Paper



Long noncoding RNAs (lncRNAs) play an important role in the pathogenesis of many human diseases. In this study, we provide the description of genome-wide lncRNA expression in the lung tissue of non-smokers without Chronic obstructive pulmonary disease (COPD), of smokers without COPD and of smokers with COPD.


RNA was extracted from human lung tissue and analysed using an Agilent Human lncRNA + mRNA Array v2.0 system.


39,253 distinct lncRNA transcripts were detected in the lung tissues of all subjects. In smokers without COPD 87 lncRNAs were significantly up-regulated and 244 down-regulated compared to non-smokers without COPD with RNA50010|UCSC-9199-1005 and RNA58351| CombinedLit_316_550, the most over- and under-regulated, respectively. In contrast, in COPD patients 120 lncRNAs were over-expressed and 43 under-expressed compared with smokers without COPD with RNA44121|UCSC-2000-3182 and RNA43510|UCSC-1260-3754 being the most over- and under-regulated, respectively. Gene Ontology (GO) and pathway analysis indicated that cigarette smoking was associated with activation of metabolic pathways, whereas COPD transcripts were associated with ‘hematopoietic cell lineage’, intermediary metabolism and immune system processes.


We conclude that the altered expression of lncRNAs might play partial role in pathways implicated in COPD onset and progression such as intermediary metabolism and the immune response.


Long noncoding RNA COPD Microarray analysis Inflammation 



This study was helped by Dr. Liang Chen and Dr. Quan Zhu for the clinical information support. This study was supported by the National Natural Science Foundation of China (81070025, 81470237), Jiangsu Health Promotion Project, and the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD, JX10231801).

Conflict of interest

The authors have declared that no competing interests exist.

Supplementary material

11_2014_790_MOESM1_ESM.docx (13 kb)
Supplementary material 1 (DOCX 12 kb)
11_2014_790_MOESM2_ESM.xlsx (11 kb)
Supplementary material 2 (XLSX 10 kb)
11_2014_790_MOESM3_ESM.xlsx (8 mb)
Supplementary material 3 (XLSX 8157 kb)
11_2014_790_MOESM4_ESM.xlsx (73 kb)
Supplementary material 4 (XLSX 73 kb)
11_2014_790_MOESM5_ESM.docx (14 kb)
Supplementary material 5 (DOCX 13 kb)
11_2014_790_MOESM6_ESM.xlsx (42 kb)
Supplementary material 6 (XLSX 42 kb)
11_2014_790_MOESM7_ESM.xlsx (15 kb)
Supplementary material 7 (XLSX 15 kb)
11_2014_790_MOESM8_ESM.xlsx (11 mb)
Supplementary material 8 (XLSX 11259 kb)
11_2014_790_MOESM9_ESM.xlsx (79 kb)
Supplementary material 9 (XLSX 78 kb)
11_2014_790_MOESM10_ESM.xlsx (55 kb)
Supplementary material 10 (XLSX 55 kb)
11_2014_790_MOESM11_ESM.xlsx (11 kb)
Supplementary material 11 (XLSX 11 kb)
11_2014_790_MOESM12_ESM.xlsx (14 kb)
Supplementary material 12 (XLSX 14 kb)
11_2014_790_MOESM13_ESM.xlsx (13 kb)
Supplementary material 13 (XLSX 12 kb)
11_2014_790_MOESM14_ESM.docx (14 kb)
Supplementary material 14 (DOCX 14 kb)
11_2014_790_MOESM15_ESM.xlsx (10 kb)
Supplementary material 15 (XLSX 9 kb)


  1. 1.
    Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. 2014.Google Scholar
  2. 2.
    Carr SJ, Hill K, Brooks D, Goldstein RS. Pulmonary rehabilitation after acute exacerbation of chronic obstructive pulmonary disease in patients who previously completed a pulmonary rehabilitation program. J Cardiopulm Rehabil Prev. 2009;29:318–24.PubMedCrossRefGoogle Scholar
  3. 3.
    Sullivan SD, Ramsey SD, Lee TA. The economic burden of COPD. Chest. 2000;117:5S–9S.PubMedCrossRefGoogle Scholar
  4. 4.
    Lokke A, Lange P, Scharling H, Fabricius P, Vestbo J. Developing COPD: a 25 year follow up study of the general population. Thorax. 2006;61:935–9.PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Costa FF. Non-coding RNAs, epigenetics and complexity. Gene. 2008;410:9–17.PubMedCrossRefGoogle Scholar
  6. 6.
    Faghihi MA, Wahlestedt C. Regulatory roles of natural antisense transcripts. Nat Rev Mol Cell Biol. 2009;10:637–43.PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    Ponting CP, Oliver PL, Reik W. Evolution and functions of long noncoding RNAs. Cell. 2009;136:629–41.PubMedCrossRefGoogle Scholar
  8. 8.
    Wang KC, Chang HY. Molecular mechanisms of long noncoding RNAs. Mol Cell. 2011;43:904–14.PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Brockdorff N, Ashworth A, Kay GF, McCabe VM, Norris DP, Cooper PJ, et al. The product of the mouse Xist gene is a 15 kb inactive X-specific transcript containing no conserved ORF and located in the nucleus. Cell. 1992;71:515–26.PubMedCrossRefGoogle Scholar
  10. 10.
    Brown CJ, Hendrich BD, Rupert JL, Lafreniere RG, Xing Y, Lawrence J, et al. The human XIST gene: analysis of a 17 kb inactive X-specific RNA that contains conserved repeats and is highly localized within the nucleus. Cell. 1992;71:527–42.PubMedCrossRefGoogle Scholar
  11. 11.
    Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, et al. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 2010;464:1071–6.PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Guttman M, Donaghey J, Carey BW, Garber M, Grenier JK, Munson G, et al. lincRNAs act in the circuitry controlling pluripotency and differentiation. Nature. 2011;477:295–300.PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Khalil AM, Guttman M, Huarte M, Garber M, Raj A, Rivea Morales D, et al. Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. Proc Nat Acad Sci USA. 2009;106:11667–72.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Wapinski O, Chang HY. Long noncoding RNAs and human disease. Trends Cell Biol. 2011;21:354–61.PubMedCrossRefGoogle Scholar
  15. 15.
    Massone S, Vassallo I, Fiorino G, Castelnuovo M, Barbieri F, Borghi R, et al. 17A, a novel non-coding RNA, regulates GABA B alternative splicing and signaling in response to inflammatory stimuli and in Alzheimer disease. Neurobiol Dis. 2011;41:308–17.PubMedCrossRefGoogle Scholar
  16. 16.
    Thai P, Statt S, Chen CH, Liang E, Campbell C, Wu R. Characterization of a novel long non-coding RNA, SCAL1, induced by cigarette smoke and elevated in lung cancer cell lines. Am J Respir Cell Mol Biol. 2013;49:204–11.PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Orom UA, Derrien T, Beringer M, Gumireddy K, Gardini A, Bussotti G, et al. Long noncoding RNAs with enhancer-like function in human cells. Cell. 2010;143:46–58.PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Patterson TA, Lobenhofer EK, Fulmer-Smentek SB, Collins PJ, Chu TM, Bao W, et al. Performance comparison of one-color and two-color platforms within the MicroArray Quality Control (MAQC) project. Nat Biotechnol. 2006;24:1140–50.PubMedCrossRefGoogle Scholar
  19. 19.
    Barabasi AL, Oltvai ZN. Network biology: understanding the cell’s functional organization. Nat Rev Genet. 2004;5:101–13.PubMedCrossRefGoogle Scholar
  20. 20.
    Pfaffl MW. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 2001;29:e45.PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Motz GT, Eppert BL, Sun G, Wesselkamper SC, Linke MJ, Deka R, et al. Persistence of lung CD8 T cell oligoclonal expansions upon smoking cessation in a mouse model of cigarette smoke-induced emphysema (Baltimore, Md : 1950). J Immunol. 2008;181:8036–43.PubMedCrossRefGoogle Scholar
  22. 22.
    Motz GT, Eppert BL, Wesselkamper SC, Flury JL, Borchers MT. Chronic cigarette smoke exposure generates pathogenic T cells capable of driving COPD-like disease in Rag2-/- mice. Am J Respir Crit Care Med. 2010;181:1223–33.PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Sullivan AK, Simonian PL, Falta MT, Mitchell JD, Cosgrove GP, Brown KK, et al. Oligoclonal CD4 + T cells in the lungs of patients with severe emphysema. Am J Respir Crit Care Med. 2005;172:590–6.PubMedCentralPubMedCrossRefGoogle Scholar
  24. 24.
    Lee SH, Goswami S, Grudo A, Song LZ, Bandi V, Goodnight-White S, et al. Antielastin autoimmunity in tobacco smoking-induced emphysema. Nat Med. 2007;13:567–9.PubMedCrossRefGoogle Scholar
  25. 25.
    Rovina N, Koutsoukou A, Koulouris NG. Inflammation and Immune Response in COPD: where do we stand? Mediators Inflamm. 2013;2013:413735.PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Hukkanen J, Pelkonen O, Hakkola J, Raunio H. Expression and regulation of xenobiotic-metabolizing cytochrome P450 (CYP) enzymes in human lung. Crit Rev Toxicol. 2002;32:391–411.PubMedCrossRefGoogle Scholar
  27. 27.
    Engstrom G, Segelstorm N, Ekberg-Aronsson M, Nilsson PM, Lindgarde F, Lofdahl CG. Plasma markers of inflammation and incidence of hospitalisations for COPD: results from a population-based cohort study. Thorax. 2009;64:211–5.PubMedCrossRefGoogle Scholar
  28. 28.
    Barnes PJ, Shapiro SD, Pauwels RA. Chronic obstructive pulmonary disease: molecular and cellular mechanisms. Eur Respir J. 2003;22:672–88.PubMedCrossRefGoogle Scholar
  29. 29.
    Ferrari R, Tanni SE, Caram LM, Correa C, Correa CR, Godoy I. Three-year follow-up of Interleukin 6 and C-reactive protein in chronic obstructive pulmonary disease. Respir Res. 2013;14:24.PubMedCentralPubMedCrossRefGoogle Scholar
  30. 30.
    Perry MM, Baker JE, Gibeon DS, Adcock IM, Chung KF. Airway smooth muscle hyperproliferation is regulated by microRNA-221 in severe asthma. Am J Respir Cell Mol Biol. 2014;50:7–17.PubMedCentralPubMedGoogle Scholar
  31. 31.
    Sandilands A, Smith FJ, Lunny DP, Campbell LE, Davidson KM, Maccallum SF, et al. Generation and characterisation of keratin 7 (k7) knockout mice. PLoS One. 2013;8:e64404.PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer Basel 2014

Authors and Affiliations

  • Hui Bi
    • 1
  • Ji Zhou
    • 1
  • Dandan Wu
    • 1
  • Wei Gao
    • 1
  • Lingling Li
    • 1
  • Like Yu
    • 2
  • Feng Liu
    • 2
  • Mao Huang
    • 1
  • Ian M. Adcock
    • 3
  • Peter J. Barnes
    • 3
  • Xin Yao
    • 1
    Email author
  1. 1.Department of Respiratory MedicineThe First Affiliated Hospital of Nanjing Medical UniversityNanjingChina
  2. 2.Department of Respiratory MedicineNanjing Chest HospitalNanjingChina
  3. 3.Airway Disease SectionNational Heart and Lung Institute, Imperial CollegeLondonUK

Personalised recommendations