Abstract
Objective
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.
Methods
RNA was extracted from human lung tissue and analysed using an Agilent Human lncRNA + mRNA Array v2.0 system.
Results
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.
Conclusions
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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. 2014.
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.
Sullivan SD, Ramsey SD, Lee TA. The economic burden of COPD. Chest. 2000;117:5S–9S.
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.
Costa FF. Non-coding RNAs, epigenetics and complexity. Gene. 2008;410:9–17.
Faghihi MA, Wahlestedt C. Regulatory roles of natural antisense transcripts. Nat Rev Mol Cell Biol. 2009;10:637–43.
Ponting CP, Oliver PL, Reik W. Evolution and functions of long noncoding RNAs. Cell. 2009;136:629–41.
Wang KC, Chang HY. Molecular mechanisms of long noncoding RNAs. Mol Cell. 2011;43:904–14.
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.
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.
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.
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.
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.
Wapinski O, Chang HY. Long noncoding RNAs and human disease. Trends Cell Biol. 2011;21:354–61.
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.
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.
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.
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.
Barabasi AL, Oltvai ZN. Network biology: understanding the cell’s functional organization. Nat Rev Genet. 2004;5:101–13.
Pfaffl MW. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 2001;29:e45.
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.
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.
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.
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.
Rovina N, Koutsoukou A, Koulouris NG. Inflammation and Immune Response in COPD: where do we stand? Mediators Inflamm. 2013;2013:413735.
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.
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.
Barnes PJ, Shapiro SD, Pauwels RA. Chronic obstructive pulmonary disease: molecular and cellular mechanisms. Eur Respir J. 2003;22:672–88.
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.
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.
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.
Acknowledgements
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.
Author information
Authors and Affiliations
Corresponding author
Additional information
Responsible Editor: Graham R. Wallace.
H. Bi and J. Zhou contributed equally to this work.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Bi, H., Zhou, J., Wu, D. et al. Microarray analysis of long non-coding RNAs in COPD lung tissue. Inflamm. Res. 64, 119–126 (2015). https://doi.org/10.1007/s00011-014-0790-9
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00011-014-0790-9