Skip to main content
SpringerLink
Log in

MicroRNAs in the Lung

  • Chapter
  • First Online:
Book cover MicroRNA Cancer Regulation

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 774))

Abstract

The lung constitutes one of the most delicate tissue structures in mammalian organisms to accomplish the vital function of gas exchange. On the other hand, its immense surface area, necessary in this context, exhibits the first line of defense against a variety of pro-inflammatory stimuli.

MicroRNAs (miRNAs) are a class of post-transcriptional regulators that revolutionized our view of gene expression regulation. By now, it is well established that miRNAs impair all known cellular and developmental processes. Extensive research over the last years revealed not only a fundamental role for miRNAs in lung development and homeostasis, but also in the process of lung inflammation. Lung inflammation occurs in response to stimuli very different in nature (e.g., physical, radioactive, infective, pro-allergenic, or toxic), and in some cases becomes manifest in chronic diseases (e.g., chronic bronchitis/chronic obstructive pulmonary disease (COPD), asthma and allergic airway diseases) or even lung cancer.

This review chapter will briefly describe the current knowledge concerning miRNA expression and their exerted target regulation in the course of lung inflammation and lung cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Lee RC, Feinbaum RL, Ambros V (1993) The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75(5):843–854

    Article  CAS  PubMed  Google Scholar 

  2. Wightman B, Ha I, Ruvkun G (1993) Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell 75(5):855–862

    Article  CAS  PubMed  Google Scholar 

  3. Moss EG, Lee RC, Ambros V (1997) The cold shock domain protein LIN-28 controls developmental timing in C. elegans and is regulated by the lin-4 RNA. Cell 88(5):637–646

    Article  CAS  PubMed  Google Scholar 

  4. Lu J, Qian J, Chen F, Tang X, Li C, Cardoso WV (2005) Differential expression of components of the microRNA machinery during mouse organogenesis. Biochem Biophys Res Commun 334(2):319–323

    Article  PubMed  Google Scholar 

  5. Harris KS, Zhang Z, McManus MT, Harfe BD, Sun X (2006) Dicer function is essential for lung epithelium morphogenesis. Proc Natl Acad Sci USA 103(7):2208–2213

    Article  CAS  PubMed  Google Scholar 

  6. Williams AE, Moschos SA, Perry MM, Barnes PJ, Lindsay MA (2007) Maternally imprinted microRNAs are differentially expressed during mouse and human lung development. Dev Dyn 236(2):572–580

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Williams AE, Perry MM, Moschos SA, Lindsay MA (2007) MicroRNA expression in the aging mouse lung. BMC Genomics 8:172

    Article  PubMed Central  PubMed  Google Scholar 

  8. Lu Y, Thomson JM, Wong HY, Hammond SM, Hogan BL (2007) Transgenic over-expression of the microRNA miR-17-92 cluster promotes proliferation and inhibits differentiation of lung epithelial progenitor cells. Dev Biol 310(2):442–453

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Ventura A, Young AG, Winslow MM, Lintault L, Meissner A, Erkeland SJ, Newman J, Bronson RT, Crowley D, Stone JR et al (2008) Targeted deletion reveals essential and overlapping functions of the miR-17 through 92 family of miRNA clusters. Cell 132(5):875–886

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Carraro G, El-Hashash A, Guidolin D, Tiozzo C, Turcatel G, Young BM, De Langhe SP, Bellusci S, Shi W, Parnigotto PP et al (2009) MiR-17 family of microRNAs controls FGF10-mediated embryonic lung epithelial branching morphogenesis through MAPK14 and STAT3 regulation of E-Cadherin distribution. Dev Biol 333(2):238–250

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Bhaskaran M, Wang Y, Zhang H, Weng T, Baviskar P, Guo Y, Gou D, Liu L (2009) MicroRNA-127 modulates fetal lung development. Physiol Genomics 37(3):268–278

    Article  CAS  PubMed  Google Scholar 

  12. Johnson CD, Esquela-Kerscher A, Stefani G, Byrom M, Kelnar K, Ovcharenko D, Wilson M, Wang X, Shelton J, Shingara J et al (2007) The let-7 microRNA represses cell proliferation pathways in human cells. Cancer Res 67(16):7713–7722

    Article  CAS  PubMed  Google Scholar 

  13. Fabbri M, Garzon R, Cimmino A, Liu Z, Zanesi N, Callegari E, Liu S, Alder H, Costinean S, Fernandez-Cymering C et al (2007) MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B. Proc Natl Acad Sci USA 104(40):15805–15810

    Article  CAS  PubMed  Google Scholar 

  14. Johnnidis JB, Harris MH, Wheeler RT, Stehling-Sun S, Lam MH, Kirak O, Brummelkamp TR, Fleming MD, Camargo FD (2008) Regulation of progenitor cell proliferation and granulocyte function by microRNA-223. Nature 451(7182):1125–1129

    Article  CAS  PubMed  Google Scholar 

  15. Rodriguez A, Vigorito E, Clare S, Warren MV, Couttet P, Soond DR, van Dongen S, Grocock RJ, Das PP, Miska EA et al (2007) Requirement of bic/microRNA-155 for normal immune function. Science 316(5824):608–611

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Chen CZ, Li L, Lodish HF, Bartel DP (2004) MicroRNAs modulate hematopoietic lineage differentiation. Science 303(5654):83–86

    Article  CAS  PubMed  Google Scholar 

  17. Havelange V, Garzon R (2010) MicroRNAs: emerging key regulators of hematopoiesis. Am J Hematol 85(12):935–942

    Article  CAS  PubMed  Google Scholar 

  18. Malumbres R, Lossos IS (2010) Expression of miRNAs in lymphocytes: a review. Methods Mol Biol 667:129–143

    Article  CAS  PubMed  Google Scholar 

  19. Navarro F, Lieberman J (2010) Small RNAs guide hematopoietic cell differentiation and function. J Immunol 184(11):5939–5947

    Article  CAS  PubMed  Google Scholar 

  20. Taganov KD, Boldin MP, Chang KJ, Baltimore D (2006) NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci USA 103(33):12481–12486

    Article  CAS  PubMed  Google Scholar 

  21. O’Connell RM, Taganov KD, Boldin MP, Cheng G, Baltimore D (2007) MicroRNA-155 is induced during the macrophage inflammatory response. Proc Natl Acad Sci USA 104(5):1604–1609

    Article  PubMed  Google Scholar 

  22. Tili E, Michaille JJ, Cimino A, Costinean S, Dumitru CD, Adair B, Fabbri M, Alder H, Liu CG, Calin GA et al (2007) Modulation of miR-155 and miR-125b levels following lipopolysaccharide/TNF-alpha stimulation and their possible roles in regulating the response to endotoxin shock. J Immunol 179(8):5082–5089

    CAS  PubMed  Google Scholar 

  23. Moschos SA, Williams AE, Perry MM, Birrell MA, Belvisi MG, Lindsay MA (2007) Expression profiling in vivo demonstrates rapid changes in lung microRNA levels following lipopolysaccharide-induced inflammation but not in the anti-inflammatory action of glucocorticoids. BMC Genomics 8:240

    Article  PubMed Central  PubMed  Google Scholar 

  24. Perry MM, Moschos SA, Williams AE, Shepherd NJ, Larner-Svensson HM, Lindsay MA (2008) Rapid changes in microRNA-146a expression negatively regulate the IL-1beta-induced inflammatory response in human lung alveolar epithelial cells. J Immunol 180(8):5689–5698

    CAS  PubMed Central  PubMed  Google Scholar 

  25. Perry MM, Williams AE, Tsitsiou E, Larner-Svensson HM, Lindsay MA (2009) Divergent intracellular pathways regulate interleukin-1beta-induced miR-146a and miR-146b expression and chemokine release in human alveolar epithelial cells. FEBS Lett 583(20):3349–3355

    Article  CAS  PubMed  Google Scholar 

  26. McDonough JE, Yuan R, Suzuki M, Seyednejad N, Elliott WM, Sanchez PG, Wright AC, Gefter WB, Litzky L, Coxson HO et al (2011) Small-airway obstruction and emphysema in chronic obstructive pulmonary disease. N Engl J Med 365(17):1567–1575

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Sethi S, Murphy TF (2008) Infection in the pathogenesis and course of chronic obstructive pulmonary disease. N Engl J Med 359(22):2355–2365

    Article  CAS  PubMed  Google Scholar 

  28. Izzotti A, Calin GA, Arrigo P, Steele VE, Croce CM, De Flora S (2009) Downregulation of microRNA expression in the lungs of rats exposed to cigarette smoke. FASEB J 23(3):806–812

    Article  CAS  PubMed  Google Scholar 

  29. Izzotti A, Calin GA, Steele VE, Croce CM, De Flora S (2009) Relationships of microRNA expression in mouse lung with age and exposure to cigarette smoke and light. FASEB J 23(9):3243–3250

    Article  CAS  PubMed  Google Scholar 

  30. Schembri F, Sridhar S, Perdomo C, Gustafson AM, Zhang X, Ergun A, Lu J, Liu G, Bowers J, Vaziri C et al (2009) MicroRNAs as modulators of smoking-induced gene expression changes in human airway epithelium. Proc Natl Acad Sci USA 106(7):2319–2324

    Article  CAS  PubMed  Google Scholar 

  31. Davidson MR, Larsen JE, Yang IA, Hayward NK, Clarke BE, Duhig EE, Passmore LH, Bowman RV, Fong KM (2010) MicroRNA-218 is deleted and downregulated in lung squamous cell carcinoma. PLoS One 5(9):e12560

    Article  PubMed Central  PubMed  Google Scholar 

  32. Sato T, Liu X, Nelson A, Nakanishi M, Kanaji N, Wang X, Kim M, Li Y, Sun J, Michalski J et al (2010) Reduced miR-146a increases prostaglandin Ein chronic obstructive pulmonary disease fibroblasts. Am J Respir Crit Care Med 182(8):1020–1029

    Article  CAS  PubMed  Google Scholar 

  33. Togo S, Holz O, Liu X, Sugiura H, Kamio K, Wang X, Kawasaki S, Ahn Y, Fredriksson K, Skold CM et al (2008) Lung fibroblast repair functions in patients with chronic obstructive pulmonary disease are altered by multiple mechanisms. Am J Respir Crit Care Med 178(3):248–260

    Article  CAS  PubMed  Google Scholar 

  34. Pottelberge GR, Mestdagh P, Bracke KR, Thas O, Durme YM, Joos GF, Vandesompele J, Brusselle GG (2011) MicroRNA expression in induced sputum of smokers and patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 183(7):898–906

    Article  PubMed  Google Scholar 

  35. Mattes J, Collison A, Plank M, Phipps S, Foster PS (2009) Antagonism of microRNA-126 suppresses the effector function of TH2 cells and the development of allergic airways disease. Proc Natl Acad Sci USA 106(44):18704–18709

    Article  CAS  PubMed  Google Scholar 

  36. Collison A, Mattes J, Plank M, Foster PS (2011) Inhibition of house dust mite-induced allergic airways disease by antagonism of microRNA-145 is comparable to glucocorticoid treatment. J Allergy Clin Immunol 128(1):160–167, e164

    Article  CAS  PubMed  Google Scholar 

  37. Lu TX, Munitz A, Rothenberg ME (2009) MicroRNA-21 is up-regulated in allergic airway inflammation and regulates IL-12p35 expression. J Immunol 182(8):4994–5002

    Article  CAS  PubMed  Google Scholar 

  38. Williams AE, Larner-Svensson H, Perry MM, Campbell GA, Herrick SE, Adcock IM, Erjefalt JS, Chung KF, Lindsay MA (2009) MicroRNA expression profiling in mild asthmatic human airways and effect of corticosteroid therapy. PLoS One 4(6):e5889

    Article  PubMed Central  PubMed  Google Scholar 

  39. Polikepahad S, Knight JM, Naghavi AO, Oplt T, Creighton CJ, Shaw C, Benham AL, Kim J, Soibam B, Harris RA et al (2010) Proinflammatory role for let-7 microRNAS in experimental asthma. J Biol Chem 285(39):30139–30149

    Article  CAS  PubMed  Google Scholar 

  40. Kumar M, Ahmad T, Sharma A, Mabalirajan U, Kulshreshtha A, Agrawal A, Ghosh B (2011) Let-7 microRNA-mediated regulation of IL-13 and allergic airway inflammation. J Allergy Clin Immunol 128(5):1077–1085, e1071-1010

    Article  CAS  PubMed  Google Scholar 

  41. Garbacki N, Di Valentin E, Huynh-Thu VA, Geurts P, Irrthum A, Crahay C, Arnould T, Deroanne C, Piette J, Cataldo D et al (2011) MicroRNAs profiling in murine models of acute and chronic asthma: a relationship with mRNAs targets. PLoS One 6(1):e16509

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  42. Oglesby IK, Bray IM, Chotirmall SH, Stallings RL, O’Neill SJ, McElvaney NG, Greene CM (2010) MiR-126 is downregulated in cystic fibrosis airway epithelial cells and regulates TOM1 expression. J Immunol 184(4):1702–1709

    Article  CAS  PubMed  Google Scholar 

  43. Yamakami M, Yoshimori T, Yokosawa H (2003) Tom1, a VHS domain-containing protein, interacts with tollip, ubiquitin, and clathrin. J Biol Chem 278(52):52865–52872

    Article  CAS  PubMed  Google Scholar 

  44. Burns K, Clatworthy J, Martin L, Martinon F, Plumpton C, Maschera B, Lewis A, Ray K, Tschopp J, Volpe F (2000) Tollip, a new component of the IL-1RI pathway, links IRAK to the IL-1 receptor. Nat Cell Biol 2(6):346–351

    Article  CAS  PubMed  Google Scholar 

  45. Yamakami M, Yokosawa H (2004) Tom1 (target of Myb 1) is a novel negative regulator of interleukin-1- and tumor necrosis factor-induced signaling pathways. Biol Pharm Bull 27(4):564–566

    Article  CAS  PubMed  Google Scholar 

  46. Dean TP, Dai Y, Shute JK, Church MK, Warner JO (1993) Interleukin-8 concentrations are elevated in bronchoalveolar lavage, sputum, and sera of children with cystic fibrosis. Pediatr Res 34(2):159–161

    Article  CAS  PubMed  Google Scholar 

  47. Richman-Eisenstat JB, Jorens PG, Hebert CA, Ueki I, Nadel JA (1993) Interleukin-8: an important chemoattractant in sputum of patients with chronic inflammatory airway diseases. Am J Physiol 264(4 Pt 1):L413–418

    CAS  PubMed  Google Scholar 

  48. Bonfield TL, Panuska JR, Konstan MW, Hilliard KA, Hilliard JB, Ghnaim H, Berger M (1995) Inflammatory cytokines in cystic fibrosis lungs. Am J Respir Crit Care Med 152(6 Pt 1):2111–2118

    Article  CAS  PubMed  Google Scholar 

  49. Bhattacharyya S, Balakathiresan NS, Dalgard C, Gutti U, Armistead D, Jozwik C, Srivastava M, Pollard HB, Biswas R (2011) Elevated miR-155 promotes inflammation in cystic fibrosis by driving hyperexpression of interleukin-8. J Biol Chem 286(13):11604–11615

    Article  CAS  PubMed  Google Scholar 

  50. Gillen AE, Gosalia N, Leir SH, Harris A (2011) MicroRNA regulation of expression of the cystic fibrosis transmembrane conductance regulator gene. Biochem J 438(1):25–32

    Article  CAS  PubMed  Google Scholar 

  51. Megiorni F, Cialfi S, Dominici C, Quattrucci S, Pizzuti A (2011) Synergistic post-transcriptional regulation of the cystic fibrosis transmembrane conductance regulator (CFTR) by miR-101 and miR-494 specific binding. PLoS One 6(10):e26601

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  52. Karube Y, Tanaka H, Osada H, Tomida S, Tatematsu Y, Yanagisawa K, Yatabe Y, Takamizawa J, Miyoshi S, Mitsudomi T et al (2005) Reduced expression of Dicer associated with poor prognosis in lung cancer patients. Cancer Sci 96(2):111–115

    Article  CAS  PubMed  Google Scholar 

  53. Bishop JA, Benjamin H, Cholakh H, Chajut A, Clark DP, Westra WH (2010) Accurate classification of non-small cell lung carcinoma using a novel microRNA-based approach. Clin Cancer Res 16(2):610–619

    Article  CAS  PubMed  Google Scholar 

  54. Qi J, Rice SJ, Salzberg AC, Runkle EA, Liao J, Zander DS, Mu D (2012) MiR-365 regulates lung cancer and developmental gene thyroid transcription factor 1. Cell Cycle 11(1):177–186

    Article  CAS  PubMed  Google Scholar 

  55. Incoronato M, Urso L, Portela A, Laukkanen MO, Soini Y, Quintavalle C, Keller S, Esteller M, Condorelli G (2011) Epigenetic regulation of miR-212 expression in lung cancer. PLoS One 6(11):e27722

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  56. Feng B, Wang R, Chen LB (2012, epub was 2011) MiR-100 resensitizes docetaxel-resistant human lung adenocarcinoma cells (SPC-A1) to docetaxel by targeting Plk1. Cancer Lett 317:184–191

    Article  PubMed  Google Scholar 

  57. Feng B, Wang R, Song HZ, Chen LB (2012) MicroRNA-200b reverses chemoresistance of docetaxel-resistant human lung adenocarcinoma cells by targeting E2F3. Cancer 118:3365–3376

    Article  CAS  PubMed  Google Scholar 

  58. Garofalo M, Romano G, Di Leva G, Nuovo G, Jeon YJ, Ngankeu A, Sun J, Lovat F, Alder H, Condorelli G et al (2011) EGFR and MET receptor tyrosine kinase-altered microRNA expression induces tumorigenesis and gefitinib resistance in lung cancers. Nat Med 18:74–82

    Article  CAS  Google Scholar 

  59. Yang Y, Ahn YH, Gibbons DL, Zang Y, Lin W, Thilaganathan N, Alvarez CA, Moreira DC, Creighton CJ, Gregory PA et al (2011) The Notch ligand Jagged2 promotes lung adenocarcinoma metastasis through a miR-200-dependent pathway in mice. J Clin Invest 121(4):1373–1385

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  60. Png KJ, Halberg N, Yoshida M, Tavazoie SF (2011) A microRNA regulon that mediates endothelial recruitment and metastasis by cancer cells. Nature 481:190–194

    Article  CAS  Google Scholar 

  61. Chen LT, Xu SD, Xu H, Zhang JF, Ning JF, Wang SF (2012) MicroRNA-378 is associated with non-small cell lung cancer brain metastasis by promoting cell migration, invasion and tumor angiogenesis. Med Oncol 29:1673–1680

    Article  CAS  PubMed  Google Scholar 

  62. Babar IA, Czochor J, Steinmetz A, Weidhaas JB, Glazer PM, Slack FJ (2011) Inhibition of hypoxia-induced miR-155 radiosensitizes hypoxic lung cancer cells. Cancer Biol Ther 12(10):908–914

    Article  CAS  PubMed  Google Scholar 

  63. Russ R, Slack FJ (2012) Cigarette-smoke-induced dysregulation of MicroRNA expression and its role in lung carcinogenesis. Pulm Med 2012:791234

    PubMed Central  PubMed  Google Scholar 

  64. Lodes MJ, Caraballo M, Suciu D, Munro S, Kumar A, Anderson B (2009) Detection of cancer with serum miRNAs on an oligonucleotide microarray. PLoS One 4(7):e6229

    Article  PubMed Central  PubMed  Google Scholar 

  65. Chen X, Ba Y, Ma L, Cai X, Yin Y, Wang K, Guo J, Zhang Y, Chen J, Guo X et al (2008) Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res 18(10):997–1006

    Article  CAS  PubMed  Google Scholar 

  66. Rabinowits G, Gercel-Taylor C, Day JM, Taylor DD, Kloecker GH (2009) Exosomal microRNA: a diagnostic marker for lung cancer. Clin Lung Cancer 10(1):42–46

    Article  CAS  PubMed  Google Scholar 

  67. Keller A, Leidinger P, Borries A, Wendschlag A, Wucherpfennig F, Scheffler M, Huwer H, Lenhof HP, Meese E (2009) MiRNAs in lung cancer – studying complex fingerprints in patient’s blood cells by microarray experiments. BMC Cancer 9:353

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgements

We thank many collaborators for fruitful discussion, especially Annalisa Marsico, Julio Vera Gonzales, Martin Vingron, and Xin Lai. Part of this work has been funded by BMBF (Forsys Lung - FKZ 0315256) and DFG (SFB/TR-84, IRTG 1673) to B.S. We would like to apologize to all colleagues whose excellent contributions to the field could not be included in this text due to space constraints.

Author information

Authors and Affiliations

  1. Department of Molecular Pulmonology, German Center for Lung Research, Universities of Giessen & Marburg Lung Center, Philipps-University Marburg, Hans-Meerwein-Str. 2, 35043, Marburg, Germany

    Alexandra Sittka & Bernd Schmeck

Authors
  1. Alexandra Sittka
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bernd Schmeck
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bernd Schmeck .

Editor information

Editors and Affiliations

  1. Systems Biology and Bioinformatics, University of Rostock, Rostock, Germany

    Ulf Schmitz

  2. Dept. of Systems Biology and Bioinformat, Universität Rostock Institut of Computer Science, Rostock, Germany

    Olaf Wolkenhauer

  3. Rostock, Germany

    Julio Vera

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Sittka, A., Schmeck, B. (2013). MicroRNAs in the Lung. In: Schmitz, U., Wolkenhauer, O., Vera, J. (eds) MicroRNA Cancer Regulation. Advances in Experimental Medicine and Biology, vol 774. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5590-1_7

Download citation

Publish with us

Policies and ethics

Search

Navigation