Cellular and Molecular Life Sciences

, Volume 72, Issue 18, pp 3507–3519 | Cite as

The code of non-coding RNAs in lung fibrosis

  • Huachun Cui
  • Na Xie
  • Victor J. Thannickal
  • Gang Liu
Review

Abstract

The pathogenesis of pulmonary fibrosis is a complicated and complex process that involves phenotypic abnormalities of a variety of cell types and dysregulations of multiple signaling pathways. There are numerous genetic, epigenetic and post-transcriptional mechanisms that have been identified to participate in the pathogenesis of this disease. However, efficacious therapeutics developed from these studies have been disappointingly limited. In the past several years, a group of new molecules, i.e., non-coding RNAs (ncRNAs), has been increasingly appreciated to have critical roles in the pathological progression of lung fibrosis. In this review, we summarize the recent findings on the roles of ncRNAs in the pathogenesis of this disorder. We analyze the translational potential of this group of molecules in treating lung fibrosis. We also discuss challenges and future opportunities of studying and utilizing ncRNAs in lung fibrosis.

Keywords

Idiopathic pulmonary fibrosis (IPF) microRNA Long non-coding RNA (lncRNA) 

Notes

Acknowledgments

We apologize to colleagues whose work could not be cited due to space limitations. Sources of funding: NIH grants HL114470 (VJT), HL105473 (GL) and HL076206 (GL).

Conflict of interest

None.

References

  1. 1.
    Thannickal VJ, Zhou Y, Gaggar A, Duncan SR (2014) Fibrosis: ultimate and proximate causes. J Clin Investig 124(11):4673–4677. doi: 10.1172/JCI74368 PubMedGoogle Scholar
  2. 2.
    Barkauskas CE, Noble PW (2014) Cellular mechanisms of tissue fibrosis. 7. New insights into the cellular mechanisms of pulmonary fibrosis. Am J Physiol Cell Physiol 306(11):C987–C996. doi: 10.1152/ajpcell.00321.2013 PubMedCentralPubMedGoogle Scholar
  3. 3.
    Noble PW, Barkauskas CE, Jiang D (2012) Pulmonary fibrosis: patterns and perpetrators. J Clin Investig 122(8):2756–2762. doi: 10.1172/JCI60323 PubMedCentralPubMedGoogle Scholar
  4. 4.
    Strieter RM, Mehrad B (2009) New mechanisms of pulmonary fibrosis. Chest 136(5):1364–1370. doi: 10.1378/chest.09-0510 PubMedGoogle Scholar
  5. 5.
    Wolters PJ, Collard HR, Jones KD (2014) Pathogenesis of idiopathic pulmonary fibrosis. Annual review of pathology 9:157–179. doi: 10.1146/annurev-pathol-012513-104706 PubMedCentralPubMedGoogle Scholar
  6. 6.
    Thannickal VJ (2013) Mechanistic links between aging and lung fibrosis. Biogerontology 14(6):609–615. doi: 10.1007/s10522-013-9451-6 PubMedGoogle Scholar
  7. 7.
    Lekkerkerker AN, Aarbiou J, van Es T, Janssen RA (2012) Cellular players in lung fibrosis. Curr Pharm Des 18(27):4093–4102PubMedGoogle Scholar
  8. 8.
    Chilosi M, Poletti V, Zamo A, Lestani M, Montagna L, Piccoli P, Pedron S, Bertaso M, Scarpa A, Murer B, Cancellieri A, Maestro R, Semenzato G, Doglioni C (2003) Aberrant Wnt/beta-catenin pathway activation in idiopathic pulmonary fibrosis. Am J Pathol 162(5):1495–1502PubMedCentralPubMedGoogle Scholar
  9. 9.
    Xu K, Moghal N, Egan SE (2012) Notch signaling in lung development and disease. Adv Exp Med Biol 727:89–98. doi: 10.1007/978-1-4614-0899-4_7 PubMedGoogle Scholar
  10. 10.
    Yan Z, Kui Z, Ping Z (2014) Reviews and prospectives of signaling pathway analysis in idiopathic pulmonary fibrosis. Autoimmun Rev 13(10):1020–1025. doi: 10.1016/j.autrev.2014.08.028 PubMedGoogle Scholar
  11. 11.
    Booton R, Lindsay MA (2014) Emerging role of MicroRNAs and long noncoding RNAs in respiratory disease. Chest 146(1):193–204. doi: 10.1378/chest.13-2736 PubMedGoogle Scholar
  12. 12.
    Pagdin T, Lavender P (2012) MicroRNAs in lung diseases. Thorax 67(2):183–184. doi: 10.1136/thoraxjnl-2011-200532 PubMedGoogle Scholar
  13. 13.
    Pandit KV, Milosevic J (2015) MicroRNA regulatory networks in idiopathic pulmonary fibrosis. Biochem Cell Biol Biochimie et biologie cellulaire. doi:10.1139/bcb-2014-0101Google Scholar
  14. 14.
    Pandit KV, Milosevic J, Kaminski N (2011) MicroRNAs in idiopathic pulmonary fibrosis. Transl Res J Lab Clin Med 157(4):191–199. doi: 10.1016/j.trsl.2011.01.012 Google Scholar
  15. 15.
    Taft RJ, Pang KC, Mercer TR, Dinger M, Mattick JS (2010) Non-coding RNAs: regulators of disease. J Pathol 220(2):126–139. doi: 10.1002/path.2638 PubMedGoogle Scholar
  16. 16.
    Mattick JS (2009) The genetic signatures of noncoding RNAs. PLoS Genet 5(4):e1000459. doi: 10.1371/journal.pgen.1000459 PubMedCentralPubMedGoogle Scholar
  17. 17.
    Carthew RW, Sontheimer EJ (2009) Origins and mechanisms of miRNAs and siRNAs. Cell 136(4):642–655. doi: 10.1016/j.cell.2009.01.035 PubMedCentralPubMedGoogle Scholar
  18. 18.
    Aravin AA, Hannon GJ, Brennecke J (2007) The Piwi-piRNA pathway provides an adaptive defense in the transposon arms race. Science 318(5851):761–764. doi: 10.1126/science.1146484 PubMedGoogle Scholar
  19. 19.
    Wang KC, Chang HY (2011) Molecular mechanisms of long noncoding RNAs. Mol Cell 43(6):904–914. doi: 10.1016/j.molcel.2011.08.018 PubMedCentralPubMedGoogle Scholar
  20. 20.
    Carninci P, Yasuda J, Hayashizaki Y (2008) Multifaceted mammalian transcriptome. Curr Opin Cell Biol 20(3):274–280. doi: 10.1016/j.ceb.2008.03.008 PubMedGoogle Scholar
  21. 21.
    Jacquier A (2009) The complex eukaryotic transcriptome: unexpected pervasive transcription and novel small RNAs. Nat Rev Genet 10(12):833–844. doi: 10.1038/nrg2683 PubMedGoogle Scholar
  22. 22.
    Carninci P (2009) Molecular biology: the long and short of RNAs. Nature 457(7232):974–975. doi: 10.1038/457974b PubMedGoogle Scholar
  23. 23.
    Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116(2):281–297PubMedGoogle Scholar
  24. 24.
    Bushati N, Cohen SM (2007) microRNA functions. Annu Rev Cell Dev Biol 23:175–205. doi: 10.1146/annurev.cellbio.23.090506.123406 PubMedGoogle Scholar
  25. 25.
    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):843–854PubMedGoogle Scholar
  26. 26.
    Cullen BR (2006) Viruses and microRNAs. Nat Genet 38(Suppl):S25–S30. doi: 10.1038/ng1793 PubMedGoogle Scholar
  27. 27.
    Zeng Y (2006) Principles of micro-RNA production and maturation. Oncogene 25(46):6156–6162. doi: 10.1038/sj.onc.1209908 PubMedGoogle Scholar
  28. 28.
    Cai X, Hagedorn CH, Cullen BR (2004) Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs. RNA 10(12):1957–1966. doi: 10.1261/rna.7135204 PubMedCentralPubMedGoogle Scholar
  29. 29.
    Borchert GM, Lanier W, Davidson BL (2006) RNA polymerase III transcribes human microRNAs. Nat Struct Mol Biol 13(12):1097–1101. doi: 10.1038/nsmb1167 PubMedGoogle Scholar
  30. 30.
    Kim VN (2005) MicroRNA biogenesis: coordinated cropping and dicing. Nat Rev Mol Cell Biol 6(5):376–385. doi: 10.1038/nrm1644 PubMedGoogle Scholar
  31. 31.
    Stefani G, Slack FJ (2008) Small non-coding RNAs in animal development. Nat Rev Mol Cell Biol 9(3):219–230. doi: 10.1038/nrm2347 PubMedGoogle Scholar
  32. 32.
    Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, Downing JR, Jacks T, Horvitz HR, Golub TR (2005) MicroRNA expression profiles classify human cancers. Nature 435(7043):834–838. doi: 10.1038/nature03702 PubMedGoogle Scholar
  33. 33.
    Li P, Li J, Chen T, Wang H, Chu H, Chang J, Zang W, Wang Y, Ma Y, Du Y, Zhao G, Zhang G (2014) Expression analysis of serum microRNAs in idiopathic pulmonary fibrosis. Int J Mol Med 33(6):1554–1562. doi: 10.3892/ijmm.2014.1712 PubMedGoogle Scholar
  34. 34.
    Brosius J (2005) Waste not, want not—transcript excess in multicellular eukaryotes. Trends Genet 21(5):287–288. doi: 10.1016/j.tig.2005.02.014 PubMedGoogle Scholar
  35. 35.
    Struhl K (2007) Transcriptional noise and the fidelity of initiation by RNA polymerase II. Nat Struct Mol Biol 14(2):103–105. doi: 10.1038/nsmb0207-103 PubMedGoogle Scholar
  36. 36.
    Derrien T, Johnson R, Bussotti G, Tanzer A, Djebali S, Tilgner H, Guernec G, Martin D, Merkel A, Knowles DG, Lagarde J, Veeravalli L, Ruan X, Ruan Y, Lassmann T, Carninci P, Brown JB, Lipovich L, Gonzalez JM, Thomas M, Davis CA, Shiekhattar R, Gingeras TR, Hubbard TJ, Notredame C, Harrow J, Guigo R (2012) The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression. Genome Res 22(9):1775–1789. doi: 10.1101/gr.132159.111 PubMedCentralPubMedGoogle Scholar
  37. 37.
    Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, Tsai MC, Hung T, Argani P, Rinn JL, Wang Y, Brzoska P, Kong B, Li R, West RB, van de Vijver MJ, Sukumar S, Chang HY (2010) Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature 464(7291):1071–1076. doi: 10.1038/nature08975 PubMedCentralPubMedGoogle Scholar
  38. 38.
    Yu W, Gius D, Onyango P, Muldoon-Jacobs K, Karp J, Feinberg AP, Cui H (2008) Epigenetic silencing of tumour suppressor gene p15 by its antisense RNA. Nature 451(7175):202–206. doi: 10.1038/nature06468 PubMedCentralPubMedGoogle Scholar
  39. 39.
    Loewer S, Cabili MN, Guttman M, Loh YH, Thomas K, Park IH, Garber M, Curran M, Onder T, Agarwal S, Manos PD, Datta S, Lander ES, Schlaeger TM, Daley GQ, Rinn JL (2010) Large intergenic non-coding RNA-RoR modulates reprogramming of human induced pluripotent stem cells. Nat Genet 42(12):1113–1117. doi: 10.1038/ng.710 PubMedCentralPubMedGoogle Scholar
  40. 40.
    Huarte M, Guttman M, Feldser D, Garber M, Koziol MJ, Kenzelmann-Broz D, Khalil AM, Zuk O, Amit I, Rabani M, Attardi LD, Regev A, Lander ES, Jacks T, Rinn JL (2010) A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response. Cell 142(3):409–419. doi: 10.1016/j.cell.2010.06.040 PubMedCentralPubMedGoogle Scholar
  41. 41.
    Hu W, Alvarez-Dominguez JR, Lodish HF (2012) Regulation of mammalian cell differentiation by long non-coding RNAs. EMBO Rep 13(11):971–983. doi: 10.1038/embor.2012.145 PubMedGoogle Scholar
  42. 42.
    Lee JT (2009) Lessons from X-chromosome inactivation: long ncRNA as guides and tethers to the epigenome. Genes Dev 23(16):1831–1842. doi: 10.1101/gad.1811209 PubMedCentralPubMedGoogle Scholar
  43. 43.
    Sleutels F, Zwart R, Barlow DP (2002) The non-coding Air RNA is required for silencing autosomal imprinted genes. Nature 415(6873):810–813. doi: 10.1038/415810a PubMedGoogle Scholar
  44. 44.
    Lee JT, Bartolomei MS (2013) X-inactivation, imprinting, and long noncoding rnas in health and disease. Cell 152(6):1308–1323. doi: 10.1016/j.cell.2013.02.016 PubMedGoogle Scholar
  45. 45.
    Sun L, Goff LA, Trapnell C, Alexander R, Lo KA, Hacisuleyman E, Sauvageau M, Tazon-Vega B, Kelley DR, Hendrickson DG, Yuan B, Kellis M, Lodish HF, Rinn JL (2013) Long noncoding RNAs regulate adipogenesis. Proc Natl Acad Sci USA 110(9):3387–3392. doi: 10.1073/pnas.1222643110 PubMedCentralPubMedGoogle Scholar
  46. 46.
    Sasaki YT, Ideue T, Sano M, Mituyama T, Hirose T (2009) MENepsilon/beta noncoding RNAs are essential for structural integrity of nuclear paraspeckles. Proc Natl Acad Sci USA 106(8):2525–2530. doi: 10.1073/pnas.0807899106 PubMedCentralPubMedGoogle Scholar
  47. 47.
    Song X, Cao G, Jing L, Lin S, Wang X, Zhang J, Wang M, Liu W, Lv C (2014) Analysing the relationship between lncRNA and protein-coding gene and the role of lncRNA as ceRNA in pulmonary fibrosis. J Cell Mol Med 18(6):991–1003. doi: 10.1111/jcmm.12243 PubMedCentralPubMedGoogle Scholar
  48. 48.
    Cao G, Zhang J, Wang M, Song X, Liu W, Mao C, Lv C (2013) Differential expression of long non-coding RNAs in bleomycin-induced lung fibrosis. Int J Mol Med 32(2):355–364. doi: 10.3892/ijmm.2013.1404 PubMedGoogle Scholar
  49. 49.
    Han L, Zhang EB, Yin DD, Kong R, Xu TP, Chen WM, Xia R, Shu YQ, De W (2015) Low expression of long noncoding RNA PANDAR predicts a poor prognosis of non-small cell lung cancer and affects cell apoptosis by regulating Bcl-2. Cell Death Dis 6:e1665. doi: 10.1038/cddis.2015.30 PubMedGoogle Scholar
  50. 50.
    Honeyman L, Bazett M, Tomko TG, Haston CK (2013) MicroRNA profiling implicates the insulin-like growth factor pathway in bleomycin-induced pulmonary fibrosis in mice. Fibrogenesis Tissue Repair 6(1):16. doi: 10.1186/1755-1536-6-16 PubMedGoogle Scholar
  51. 51.
    Liang H, Gu Y, Li T, Zhang Y, Huangfu L, Hu M, Zhao D, Chen Y, Liu S, Dong Y, Li X, Lu Y, Yang B, Shan H (2014) Integrated analyses identify the involvement of microRNA-26a in epithelial-mesenchymal transition during idiopathic pulmonary fibrosis. Cell Death Dis 5:e1238. doi: 10.1038/cddis.2014.207 PubMedCentralPubMedGoogle Scholar
  52. 52.
    Liu G, Friggeri A, Yang Y, Milosevic J, Ding Q, Thannickal VJ, Kaminski N, Abraham E (2010) miR-21 mediates fibrogenic activation of pulmonary fibroblasts and lung fibrosis. J Exp Med 207(8):1589–1597. doi: 10.1084/jem.20100035 PubMedCentralPubMedGoogle Scholar
  53. 53.
    Pandit KV, Corcoran D, Yousef H, Yarlagadda M, Tzouvelekis A, Gibson KF, Konishi K, Yousem SA, Singh M, Handley D, Richards T, Selman M, Watkins SC, Pardo A, Ben-Yehudah A, Bouros D, Eickelberg O, Ray P, Benos PV, Kaminski N (2010) Inhibition and role of let-7d in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 182(2):220–229. doi: 10.1164/rccm.200911-1698OC PubMedCentralPubMedGoogle Scholar
  54. 54.
    Xie T, Liang J, Guo R, Liu N, Noble PW, Jiang D (2011) Comprehensive microRNA analysis in bleomycin-induced pulmonary fibrosis identifies multiple sites of molecular regulation. Physiol Genomics 43(9):479–487. doi: 10.1152/physiolgenomics.00222.2010 PubMedCentralPubMedGoogle Scholar
  55. 55.
    Yuchuan H, Ya D, Jie Z, Jingqiu C, Yanrong L, Dongliang L, Changguo W, Kuoyan M, Guangneng L, Fang X, Lanlan T, Bo Q (2014) Circulating miRNAs might be promising biomarkers to reflect the dynamic pathological changes in smoking-related interstitial fibrosis. Toxicol Ind Health 30(2):182–191. doi: 10.1177/0748233712452606 PubMedGoogle Scholar
  56. 56.
    Cushing L, Kuang PP, Qian J, Shao F, Wu J, Little F, Thannickal VJ, Cardoso WV, Lu J (2011) miR-29 is a major regulator of genes associated with pulmonary fibrosis. Am J Respir Cell Mol Biol 45(2):287–294. doi: 10.1165/rcmb.2010-0323OC PubMedCentralPubMedGoogle Scholar
  57. 57.
    Xiao J, Meng XM, Huang XR, Chung AC, Feng YL, Hui DS, Yu CM, Sung JJ, Lan HY (2012) miR-29 inhibits bleomycin-induced pulmonary fibrosis in mice. Mol Ther J Am Soc Gene Ther 20(6):1251–1260. doi: 10.1038/mt.2012.36 Google Scholar
  58. 58.
    Montgomery RL, Yu G, Latimer PA, Stack C, Robinson K, Dalby CM, Kaminski N, van Rooij E (2014) MicroRNA mimicry blocks pulmonary fibrosis. EMBO Mol Med 6(10):1347–1356. doi: 10.15252/emmm.201303604 PubMedCentralPubMedGoogle Scholar
  59. 59.
    Parker MW, Rossi D, Peterson M, Smith K, Sikstrom K, White ES, Connett JE, Henke CA, Larsson O, Bitterman PB (2014) Fibrotic extracellular matrix activates a profibrotic positive feedback loop. J Clin Investig 124(4):1622–1635. doi: 10.1172/JCI71386 PubMedCentralPubMedGoogle Scholar
  60. 60.
    Liang H, Xu C, Pan Z, Zhang Y, Xu Z, Chen Y, Li T, Li X, Liu Y, Huangfu L, Lu Y, Zhang Z, Yang B, Gitau S, Lu Y, Shan H, Du Z (2014) The antifibrotic effects and mechanisms of microRNA-26a action in idiopathic pulmonary fibrosis. Mol Ther J Am Soc Gene Ther 22(6):1122–1133. doi: 10.1038/mt.2014.42 Google Scholar
  61. 61.
    Thuault S, Valcourt U, Petersen M, Manfioletti G, Heldin CH, Moustakas A (2006) Transforming growth factor-beta employs HMGA2 to elicit epithelial-mesenchymal transition. J Cell Biol 174(2):175–183. doi: 10.1083/jcb.200512110 PubMedCentralPubMedGoogle Scholar
  62. 62.
    Thuault S, Tan EJ, Peinado H, Cano A, Heldin CH, Moustakas A (2008) HMGA2 and Smads co-regulate SNAIL1 expression during induction of epithelial-to-mesenchymal transition. J Biol Chem 283(48):33437–33446. doi: 10.1074/jbc.M802016200 PubMedCentralPubMedGoogle Scholar
  63. 63.
    Li X, Liu L, Shen Y, Wang T, Chen L, Xu D, Wen F (2014) MicroRNA-26a modulates transforming growth factor beta-1-induced proliferation in human fetal lung fibroblasts. Biochem Biophys Res Commun 454(4):512–517. doi: 10.1016/j.bbrc.2014.10.106 PubMedGoogle Scholar
  64. 64.
    Varga J, Pasche B (2008) Antitransforming growth factor-beta therapy in fibrosis: recent progress and implications for systemic sclerosis. Curr Opin Rheumatol 20(6):720–728. doi: 10.1097/BOR.0b013e32830e48e8 PubMedCentralPubMedGoogle Scholar
  65. 65.
    Das S, Kumar M, Negi V, Pattnaik B, Prakash YS, Agrawal A, Ghosh B (2014) MicroRNA-326 regulates profibrotic functions of transforming growth factor-beta in pulmonary fibrosis. Am J Respir Cell Mol Biol 50(5):882–892. doi: 10.1165/rcmb.2013-0195OC PubMedCentralPubMedGoogle Scholar
  66. 66.
    Coward WR, Saini G, Jenkins G (2010) The pathogenesis of idiopathic pulmonary fibrosis. Ther Adv Respir Dis 4(6):367–388. doi: 10.1177/1753465810379801 PubMedGoogle Scholar
  67. 67.
    Bartis D, Mise N, Mahida RY, Eickelberg O, Thickett DR (2014) Epithelial-mesenchymal transition in lung development and disease: does it exist and is it important? Thorax 69(8):760–765. doi: 10.1136/thoraxjnl-2013-204608 PubMedGoogle Scholar
  68. 68.
    Wynn TA (2008) Cellular and molecular mechanisms of fibrosis. J Pathol 214(2):199–210. doi: 10.1002/path.2277 PubMedCentralPubMedGoogle Scholar
  69. 69.
    Huleihel L, Ben-Yehudah A, Milosevic J, Yu G, Pandit K, Sakamoto K, Yousef H, LeJeune M, Coon TA, Redinger CJ, Chensny L, Manor E, Schatten G, Kaminski N (2014) Let-7d microRNA affects mesenchymal phenotypic properties of lung fibroblasts. Am J Physiol Lung Cell Mol Physiol 306(6):L534–L542. doi: 10.1152/ajplung.00149.2013 PubMedCentralPubMedGoogle Scholar
  70. 70.
    Yang S, Banerjee S, de Freitas A, Sanders YY, Ding Q, Matalon S, Thannickal VJ, Abraham E, Liu G (2012) Participation of miR-200 in pulmonary fibrosis. Am J Pathol 180(2):484–493. doi: 10.1016/j.ajpath.2011.10.005 PubMedCentralPubMedGoogle Scholar
  71. 71.
    Berschneider B, Ellwanger DC, Baarsma HA, Thiel C, Shimbori C, White ES, Kolb M, Neth P, Konigshoff M (2014) miR-92a regulates TGF-beta1-induced WISP1 expression in pulmonary fibrosis. Int J Biochem Cell Biol 53:432–441. doi: 10.1016/j.biocel.2014.06.011 PubMedGoogle Scholar
  72. 72.
    Graham JR, Williams CM, Yang Z (2014) MicroRNA-27b targets gremlin 1 to modulate fibrotic responses in pulmonary cells. J Cell Biochem 115(9):1539–1548. doi: 10.1002/jcb.24809 PubMedGoogle Scholar
  73. 73.
    Lino Cardenas CL, Henaoui IS, Courcot E, Roderburg C, Cauffiez C, Aubert S, Copin MC, Wallaert B, Glowacki F, Dewaeles E, Milosevic J, Maurizio J, Tedrow J, Marcet B, Lo-Guidice JM, Kaminski N, Barbry P, Luedde T, Perrais M, Mari B, Pottier N (2013) miR-199a-5p Is upregulated during fibrogenic response to tissue injury and mediates TGFbeta-induced lung fibroblast activation by targeting caveolin-1. PLoS Genet 9(2):e1003291. doi: 10.1371/journal.pgen.1003291 PubMedCentralPubMedGoogle Scholar
  74. 74.
    Wang XM, Zhang Y, Kim HP, Zhou Z, Feghali-Bostwick CA, Liu F, Ifedigbo E, Xu X, Oury TD, Kaminski N, Choi AM (2006) Caveolin-1: a critical regulator of lung fibrosis in idiopathic pulmonary fibrosis. J Exp Med 203(13):2895–2906. doi: 10.1084/jem.20061536 PubMedCentralPubMedGoogle Scholar
  75. 75.
    Li P, Zhao GQ, Chen TF, Chang JX, Wang HQ, Chen SS, Zhang GJ (2013) Serum miR-21 and miR-155 expression in idiopathic pulmonary fibrosis. J Asthma 50(9):960–964. doi: 10.3109/02770903.2013.822080 PubMedGoogle Scholar
  76. 76.
    Yang S, Cui H, Xie N, Icyuz M, Banerjee S, Antony VB, Abraham E, Thannickal VJ, Liu G (2013) miR-145 regulates myofibroblast differentiation and lung fibrosis. FASEB J 27(6):2382–2391. doi: 10.1096/fj.12-219493 PubMedCentralPubMedGoogle Scholar
  77. 77.
    Xiao X, Huang C, Zhao C, Gou X, Senavirathna LK, Hinsdale M, Lloyd P, Liu L (2015) Regulation of myofibroblast differentiation by miR-424 during epithelial-to-mesenchymal transition. Arch Biochem Biophys 566:49–57. doi: 10.1016/j.abb.2014.12.007 PubMedGoogle Scholar
  78. 78.
    Izzi L, Attisano L (2004) Regulation of the TGFbeta signalling pathway by ubiquitin-mediated degradation. Oncogene 23(11):2071–2078. doi: 10.1038/sj.onc.1207412 PubMedGoogle Scholar
  79. 79.
    Tzouvelekis A, Harokopos V, Paparountas T, Oikonomou N, Chatziioannou A, Vilaras G, Tsiambas E, Karameris A, Bouros D, Aidinis V (2007) Comparative expression profiling in pulmonary fibrosis suggests a role of hypoxia-inducible factor-1alpha in disease pathogenesis. Am J Respir Crit Care Med 176(11):1108–1119. doi: 10.1164/rccm.200705-683OC PubMedGoogle Scholar
  80. 80.
    Chan SY, Loscalzo J (2010) MicroRNA-210: a unique and pleiotropic hypoxamir. Cell Cycle 9(6):1072–1083PubMedCentralPubMedGoogle Scholar
  81. 81.
    Grosso S, Doyen J, Parks SK, Bertero T, Paye A, Cardinaud B, Gounon P, Lacas-Gervais S, Noel A, Pouyssegur J, Barbry P, Mazure NM, Mari B (2013) MiR-210 promotes a hypoxic phenotype and increases radioresistance in human lung cancer cell lines. Cell Death Dis 4:e544. doi: 10.1038/cddis.2013.71 PubMedCentralPubMedGoogle Scholar
  82. 82.
    Bodempudi V, Hergert P, Smith K, Xia H, Herrera J, Peterson M, Khalil W, Kahm J, Bitterman PB, Henke CA (2014) miR-210 promotes IPF fibroblast proliferation in response to hypoxia. Am J Physiol Lung Cell Mol Physiol 307(4):L283–L294. doi: 10.1152/ajplung.00069.2014 PubMedCentralPubMedGoogle Scholar
  83. 83.
    Hurlin PJ, Queva C, Eisenman RN (1997) Mnt: a novel Max-interacting protein and Myc antagonist. Curr Top Microbiol Immunol 224:115–121PubMedGoogle Scholar
  84. 84.
    Xia H, Khalil W, Kahm J, Jessurun J, Kleidon J, Henke CA (2010) Pathologic caveolin-1 regulation of PTEN in idiopathic pulmonary fibrosis. Am J Pathol 176(6):2626–2637. doi: 10.2353/ajpath.2010.091117 PubMedCentralPubMedGoogle Scholar
  85. 85.
    Conte E, Gili E, Fruciano M, Korfei M, Fagone E, Iemmolo M, Lo Furno D, Giuffrida R, Crimi N, Guenther A, Vancheri C (2013) PI3K p110gamma overexpression in idiopathic pulmonary fibrosis lung tissue and fibroblast cells: in vitro effects of its inhibition. Lab Invest J Tech Method Pathol 93(5):566–576. doi: 10.1038/labinvest.2013.6
  86. 86.
    Lu Y, Azad N, Wang L, Iyer AK, Castranova V, Jiang BH, Rojanasakul Y (2010) Phosphatidylinositol-3-kinase/akt regulates bleomycin-induced fibroblast proliferation and collagen production. Am J Respir Cell Mol Biol 42(4):432–441. doi: 10.1165/rcmb.2009-0002OC PubMedCentralPubMedGoogle Scholar
  87. 87.
    Huang H, Tindall DJ (2007) Dynamic FoxO transcription factors. J Cell Sci 120(Pt 15):2479–2487. doi: 10.1242/jcs.001222 PubMedGoogle Scholar
  88. 88.
    Nho RS, Hergert P (2014) FoxO3a and disease progression. World J Biol Chem 5(3):346–354. doi: 10.4331/wjbc.v5.i3.346 PubMedCentralPubMedGoogle Scholar
  89. 89.
    Nho RS, Hergert P, Kahm J, Jessurun J, Henke C (2011) Pathological alteration of FoxO3a activity promotes idiopathic pulmonary fibrosis fibroblast proliferation on type i collagen matrix. Am J Pathol 179(5):2420–2430. doi: 10.1016/j.ajpath.2011.07.020 PubMedCentralPubMedGoogle Scholar
  90. 90.
    Nho RS, Peterson M, Hergert P, Henke CA (2013) FoxO3a (Forkhead Box O3a) deficiency protects idiopathic pulmonary fibrosis (IPF) fibroblasts from type I polymerized collagen matrix-induced apoptosis via caveolin-1 (cav-1) and Fas. PLoS One 8(4):e61017. doi: 10.1371/journal.pone.0061017 PubMedCentralPubMedGoogle Scholar
  91. 91.
    Nho RS, Im J, Ho YY, Hergert P (2014) MicroRNA-96 inhibits FoxO3a function in IPF fibroblasts on type I collagen matrix. Am J Physiol Lung Cell Mol Physiol 307(8):L632–L642. doi: 10.1152/ajplung.00127.2014 PubMedGoogle Scholar
  92. 92.
    Yan X, Chen X, Liang H, Deng T, Chen W, Zhang S, Liu M, Gao X, Liu Y, Zhao C, Wang X, Wang N, Li J, Liu R, Zen K, Zhang CY, Liu B, Ba Y (2014) miR-143 and miR-145 synergistically regulate ERBB3 to suppress cell proliferation and invasion in breast cancer. Mol Cancer 13:220. doi: 10.1186/1476-4598-13-220 PubMedCentralPubMedGoogle Scholar
  93. 93.
    Mendell JT (2008) miRiad roles for the miR-17-92 cluster in development and disease. Cell 133(2):217–222. doi: 10.1016/j.cell.2008.04.001 PubMedCentralPubMedGoogle Scholar
  94. 94.
    Milosevic J, Pandit K, Magister M, Rabinovich E, Ellwanger DC, Yu G, Vuga LJ, Weksler B, Benos PV, Gibson KF, McMillan M, Kahn M, Kaminski N (2012) Profibrotic role of miR-154 in pulmonary fibrosis. Am J Respir Cell Mol Biol 47(6):879–887. doi: 10.1165/rcmb.2011-0377OC PubMedCentralPubMedGoogle Scholar
  95. 95.
    Vickers KC, Remaley AT (2012) Lipid-based carriers of microRNAs and intercellular communication. Curr Opin Lipidol 23(2):91–97. doi: 10.1097/MOL.0b013e328350a425 PubMedGoogle Scholar
  96. 96.
    Yang G, Yang L, Wang W, Wang J, Wang J, Xu Z (2015) Discovery and validation of extracellular/circulating microRNAs during idiopathic pulmonary fibrosis disease progression. Gene 562(1):138–144. doi: 10.1016/j.gene.2015.02.065 PubMedGoogle Scholar
  97. 97.
    van Rooij E, Kauppinen S (2014) Development of microRNA therapeutics is coming of age. EMBO Mol Med 6(7):851–864. doi: 10.15252/emmm.201100899 PubMedCentralPubMedGoogle Scholar
  98. 98.
    Janssen HL, Reesink HW, Lawitz EJ, Zeuzem S, Rodriguez-Torres M, Patel K, van der Meer AJ, Patick AK, Chen A, Zhou Y, Persson R, King BD, Kauppinen S, Levin AA, Hodges MR (2013) Treatment of HCV infection by targeting microRNA. N Engl J Med 368(18):1685–1694. doi: 10.1056/NEJMoa1209026 PubMedGoogle Scholar
  99. 99.
    Peacock H, Fucini RV, Jayalath P, Ibarra-Soza JM, Haringsma HJ, Flanagan WM, Willingham A, Beal PA (2011) Nucleobase and ribose modifications control immunostimulation by a microRNA-122-mimetic RNA. J Am Chem Soc 133(24):9200–9203. doi: 10.1021/ja202492e PubMedGoogle Scholar
  100. 100.
    Li Z, Rana TM (2014) Therapeutic targeting of microRNAs: current status and future challenges. Nat Rev Drug Discov 13(8):622–638. doi: 10.1038/nrd4359 PubMedGoogle Scholar
  101. 101.
    Ebert MS, Neilson JR, Sharp PA (2007) MicroRNA sponges: competitive inhibitors of small RNAs in mammalian cells. Nat Methods 4(9):721–726. doi: 10.1038/nmeth1079 PubMedGoogle Scholar
  102. 102.
    Mukherji S, Ebert MS, Zheng GX, Tsang JS, Sharp PA, van Oudenaarden A (2011) MicroRNAs can generate thresholds in target gene expression. Nat Genet 43(9):854–859. doi: 10.1038/ng.905 PubMedCentralPubMedGoogle Scholar
  103. 103.
    Gibb EA, Brown CJ, Lam WL (2011) The functional role of long non-coding RNA in human carcinomas. Molecular cancer 10:38. doi: 10.1186/1476-4598-10-38 PubMedCentralPubMedGoogle Scholar
  104. 104.
    Barsyte-Lovejoy D, Lau SK, Boutros PC, Khosravi F, Jurisica I, Andrulis IL, Tsao MS, Penn LZ (2006) The c-Myc oncogene directly induces the H19 noncoding RNA by allele-specific binding to potentiate tumorigenesis. Cancer Res 66(10):5330–5337. doi: 10.1158/0008-5472.CAN-06-0037 PubMedGoogle Scholar
  105. 105.
    Maida Y, Yasukawa M, Furuuchi M, Lassmann T, Possemato R, Okamoto N, Kasim V, Hayashizaki Y, Hahn WC, Masutomi K (2009) An RNA-dependent RNA polymerase formed by TERT and the RMRP RNA. Nature 461(7261):230–235. doi: 10.1038/nature08283 PubMedCentralPubMedGoogle Scholar
  106. 106.
    Weinrich SL, Pruzan R, Ma L, Ouellette M, Tesmer VM, Holt SE, Bodnar AG, Lichtsteiner S, Kim NW, Trager JB, Taylor RD, Carlos R, Andrews WH, Wright WE, Shay JW, Harley CB, Morin GB (1997) Reconstitution of human telomerase with the template RNA component hTR and the catalytic protein subunit hTRT. Nat Genet 17(4):498–502. doi: 10.1038/ng1297-498 PubMedGoogle Scholar
  107. 107.
    Aalbers AM, Kajigaya S, van den Heuvel-Eibrink MM, van der Velden VH, Calado RT, Young NS (2012) Human telomere disease due to disruption of the CCAAT box of the TERC promoter. Blood 119(13):3060–3063. doi: 10.1182/blood-2011-10-383182 PubMedCentralPubMedGoogle Scholar
  108. 108.
    Batista PJ, Chang HY (2013) Long noncoding RNAs: cellular address codes in development and disease. Cell 152(6):1298–1307. doi: 10.1016/j.cell.2013.02.012 PubMedCentralPubMedGoogle Scholar
  109. 109.
    Beers MF, Morrisey EE (2011) The three R’s of lung health and disease: repair, remodeling, and regeneration. J Clin Investig 121(6):2065–2073. doi: 10.1172/JCI45961 PubMedCentralPubMedGoogle Scholar
  110. 110.
    Hecker L, Logsdon NJ, Kurundkar D, Kurundkar A, Bernard K, Hock T, Meldrum E, Sanders YY, Thannickal VJ (2014) Reversal of persistent fibrosis in aging by targeting Nox4-Nrf2 redox imbalance. Sci Transl Med 6(231):231ra247. doi: 10.1126/scitranslmed.3008182
  111. 111.
    Kottmann RM, Kulkarni AA, Smolnycki KA, Lyda E, Dahanayake T, Salibi R, Honnons S, Jones C, Isern NG, Hu JZ, Nathan SD, Grant G, Phipps RP, Sime PJ (2012) Lactic acid is elevated in idiopathic pulmonary fibrosis and induces myofibroblast differentiation via pH-dependent activation of transforming growth factor-beta. Am J Respir Crit Care Med 186(8):740–751. doi: 10.1164/rccm.201201-0084OC PubMedCentralPubMedGoogle Scholar
  112. 112.
    Tanjore H, Blackwell TS, Lawson WE (2012) Emerging evidence for endoplasmic reticulum stress in the pathogenesis of idiopathic pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol 302(8):L721–L729. doi: 10.1152/ajplung.00410.2011 PubMedCentralPubMedGoogle Scholar
  113. 113.
    Tao B, Jin W, Xu J, Liang Z, Yao J, Zhang Y, Wang K, Cheng H, Zhang X, Ke Y (2014) Myeloid-specific disruption of tyrosine phosphatase Shp2 promotes alternative activation of macrophages and predisposes mice to pulmonary fibrosis. J Immunol 193(6):2801–2811. doi: 10.4049/jimmunol.1303463 PubMedGoogle Scholar
  114. 114.
    Boon RA, Iekushi K, Lechner S, Seeger T, Fischer A, Heydt S, Kaluza D, Treguer K, Carmona G, Bonauer A, Horrevoets AJ, Didier N, Girmatsion Z, Biliczki P, Ehrlich JR, Katus HA, Muller OJ, Potente M, Zeiher AM, Hermeking H, Dimmeler S (2013) MicroRNA-34a regulates cardiac ageing and function. Nature 495(7439):107–110. doi: 10.1038/nature11919 PubMedGoogle Scholar
  115. 115.
    Gao P, Tchernyshyov I, Chang TC, Lee YS, Kita K, Ochi T, Zeller KI, De Marzo AM, Van Eyk JE, Mendell JT, Dang CV (2009) c-Myc suppression of miR-23a/b enhances mitochondrial glutaminase expression and glutamine metabolism. Nature 458(7239):762–765. doi: 10.1038/nature07823 PubMedCentralPubMedGoogle Scholar
  116. 116.
    Kalamvoki M, Du T, Roizman B (2014) Cells infected with herpes simplex virus 1 export to uninfected cells exosomes containing STING, viral mRNAs, and microRNAs. Proc Natl Acad Sci USA 111(46):E4991–E4996. doi: 10.1073/pnas.1419338111 PubMedCentralPubMedGoogle Scholar
  117. 117.
    Liu G, Abraham E (2013) MicroRNAs in immune response and macrophage polarization. Arterioscler Thromb Vasc Biol 33(2):170–177. doi: 10.1161/ATVBAHA.112.300068 PubMedCentralPubMedGoogle Scholar
  118. 118.
    Tian Y, Zhang Y, Hurd L, Hannenhalli S, Liu F, Lu MM, Morrisey EE (2011) Regulation of lung endoderm progenitor cell behavior by miR302/367. Development 138(7):1235–1245. doi: 10.1242/dev.061762 PubMedCentralPubMedGoogle Scholar

Copyright information

© Springer Basel 2015

Authors and Affiliations

  • Huachun Cui
    • 1
  • Na Xie
    • 1
  • Victor J. Thannickal
    • 1
  • Gang Liu
    • 1
  1. 1.Division of Pulmonary, Allergy, and Critical Care Medicine, Department of MedicineUniversity of Alabama at BirminghamBirminghamUSA

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