Advertisement

BioDrugs

, Volume 26, Issue 3, pp 131–141 | Cite as

MicroRNAs in Rheumatoid Arthritis

Potential Role in Diagnosis and Therapy
  • Mária FilkováEmail author
  • Astrid Jüngel
  • Renate E. Gay
  • Steffen Gay
Leading Article

Abstract

Rheumatoid arthritis (RA) is a systemic, inflammatory, autoimmune disorder with progressive articular damage that may result in lifelong disability. Although major strides in understanding the disease have been made, the pathogenesis of RA has not yet been fully elucidated. Early treatment can prevent severe disability and lead to remarkable patient benefits, although a lack of therapeutic efficiency in a considerable number of patients remains problematic.

MicroRNAs (miRNAs) are small, non-coding RNAs that, depending upon base pairing to messenger RNA (mRNA), mediate mRNA cleavage, translational repression or mRNA destabilization. As fine tuning regulators of gene expression, miRNAs are involved in crucial cellular processes and their dysregulation has been described in many cell types in different diseases. In body fluids, miRNAs are present in microvesicles or incorporated into complexes with Argonaute 2 (Ago 2) or high-density lipoproteins and show high stability. Therefore, they are of interest as potential biomarkers of disease in daily diagnostic applications. Targeting miRNAs by gain or loss of function approaches have brought therapeutic effects in various animal models.

Over the past several years it has become clear that alterations exist in the expression of miRNAs in patients with RA. Increasing numbers of studies have shown that dysregulation of miRNAs in peripheral blood mononuclear cells or isolated T lymphocytes, in synovial tissue and synovial fibroblasts that are considered key effector cells in joint destruction, contributes to inflammation, degradation of extracellular matrix and invasive behaviour of resident cells. Thereby, miRNAs maintain the pathophysiological process typical of RA.

The aim of the current review is to discuss the available evidence linking the expression of miRNAs to inflammatory and immune response in RA and their potential as biomarkers and the novel targets for treatment in patients with RA.

Keywords

Rheumatoid Arthritis Peripheral Blood Mononuclear Cell Rheumatoid Arthritis Patient Synovial Fluid Synovial Tissue 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

This work was supported by IAR-EPALINGES, FP7 Masterswitch and ARTICULUM fellowship. The authors have no conflicts of interest that are directly relevant to the content of this article.

References

  1. 1.
    Klareskog L, Catrina AI, Paget S. Rheumatoid arthritis. Lancet 2009 Feb 21; 373 (9664): 659–72PubMedGoogle Scholar
  2. 2.
    Müller-Ladner U, Pap T, Gay RE, et al. Mechanisms of disease: the molecular and cellular basis of joint destruction in rheumatoid arthritis. Nat Clin Pract Rheumatol 2005 Dec; 1 (2): 102–10PubMedGoogle Scholar
  3. 3.
    McInnes IB, Schett G. Cytokines in the pathogenesis of rheumatoid arthritis. Nat Rev Immunol 2007 Jun; 7 (6): 429–42PubMedGoogle Scholar
  4. 4.
    Ospelt C, Gay S. The role of resident synovial cells in destructive arthritis. Best Pract Res Clin Rheumatol 2008 Apr; 22 (2): 239–52PubMedGoogle Scholar
  5. 5.
    Karouzakis E, Neidhart M, Gay RE, et al. Molecular and cellular basis of rheumatoid joint destruction. Immunol Lett 2006 Jul 15; 106(1): 8–13PubMedGoogle Scholar
  6. 6.
    Müller-Ladner U, Kriegsmann J, Franklin BN, et al. Synovial fibroblasts of patients with rheumatoid arthritis attach to and invade normal human cartilage when engrafted into SCID mice. Am J Pathol 1996 Nov; 149 (5): 1607–15PubMedGoogle Scholar
  7. 7.
    Lefèvre S, Knedla A, Tennie C, et al. Synovial fibroblasts spread rheumatoid arthritis to unaffected joints. Nat Med 2009 Dec; 15 (12): 1414–20PubMedGoogle Scholar
  8. 8.
    Karouzakis E, Gay RE, Gay S, et al. Epigenetic control in rheumatoid arthritis synovial fibroblasts. Nat Rev Rheumatol 2009 May; 5 (5): 266–72PubMedGoogle Scholar
  9. 9.
    Jüngel A, Ospelt C, Gay S. What can we learn from epigenetics in the year 2009? Curr Opin Rheumatol 2010 May; 22 (3): 284–92PubMedGoogle Scholar
  10. 10.
    Trenkmann M, Brock M, Ospelt C, et al. Epigenetics in rheumatoid arthritis. Clin Rev Allergy Immunol 2010 Aug; 39 (1): 10–9PubMedGoogle Scholar
  11. 11.
    Luo X, Tsai LM, Shen N, et al. Evidence for microRNA-mediated regulation in rheumatic diseases. Ann Rheum Dis 2010 Jan; 69 Suppl. 1: i30–6PubMedGoogle Scholar
  12. 12.
    Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004 Jan 23; 116 (2): 281–97PubMedGoogle Scholar
  13. 13.
    Kim VN, Han J, Siomi MC. Biogenesis of small RNAs in animals. Nat Rev Mol Cell Biol 2009 Feb; 10 (2): 126–39PubMedGoogle Scholar
  14. 14.
    Kawamata T, Tomari Y. Making RISC. Trends Biochem Sci 2010 Jul; 35 (7): 368–76PubMedGoogle Scholar
  15. 15.
    Kwak PB, Tomari Y. The N domain of Argonaute drives duplex unwinding during RISC assembly. Nat Struct Mol Biol 2012; 19 (2): 145–51PubMedGoogle Scholar
  16. 16.
    Filipowicz W, Bhattacharyya SN, Sonenberg N. Mechanisms of posttranscriptional regulation by microRNAs: are the answers in sight? Nat Rev Genet 2008 Feb; 9 (2): 102–14PubMedGoogle Scholar
  17. 17.
    Lytle JR, Yario TA, Steitz JA. Target mRNAs are repressed as efficiently by microRNA-binding sites in the 5’ UTR as in the 3′ UTR. Proc Natl Acad Sci USA 2007 Jun 5; 104 (23): 9667–72PubMedGoogle Scholar
  18. 18.
    Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 2005 Jan 14; 120 (1): 15–20PubMedGoogle Scholar
  19. 19.
    Kloosterman WP, Wienholds E, Ketting RF, et al. Substrate requirements for let-7 function in the developing zebrafish embryo. Nucleic Acids Res 2004 Dec 7; 32 (21): 6284–91PubMedGoogle Scholar
  20. 20.
    Pillai RS, Bhattacharyya SN, Filipowicz W. Repression of protein synthesis by miRNAs: how many mechanisms? Trends Cell Biol 2007 Mar; 17 (3): 118–26PubMedGoogle Scholar
  21. 21.
    Wu L, Fan J, Belasco JG. MicroRNAs direct rapid deadenylation of mRNA. Proc Natl Acad Sci U S A 2006 Mar 14; 103 (11): 4034–9PubMedGoogle Scholar
  22. 22.
    Eulalio A, Huntzinger E, Nishihara T, et al. Deadenylation is a widespread effect of miRNA regulation. RNA 2009 Jan; 15 (1): 21–32PubMedGoogle Scholar
  23. 23.
    Behm-Ansmant I, Rehwinkel J, Doerks T, et al. mRNA degradation by miRNAs and GW182 requires both CCR4:NOT deadenylase and DCP1:DCP2 decapping complexes. Genes Dev 2006 Jul 15; 20 (14): 1885–98PubMedGoogle Scholar
  24. 24.
    Guo H, Ingolia NT, Weissman JS, et al. Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature 2010 Aug 12; 466 (7308): 835–40PubMedGoogle Scholar
  25. 25.
    Vasudevan S, Tong Y, Steitz JA. Switching from repression to activation: microRNAs can up-regulate translation. Science 2007 Dec 21; 318 (5858): 1931–4PubMedGoogle Scholar
  26. 26.
    Westholm JO, Lai EC. Mirtrons: microRNA biogenesis via splicing. Biochimie 2011 Nov; 93 (11): 1897–904PubMedGoogle Scholar
  27. 27.
    Cifuentes D, Xue H, Taylor DW, et al. A novel miRNA processing pathway independent of Dicer requires Argonaute2 catalytic activity. Science 2010 Jun 25; 328(5986): 1694–8PubMedGoogle Scholar
  28. 28.
    Cheloufi S, Dos Santos CO, Chong MM, et al. A dicer-independent miRNA biogenesis pathway that requires Ago catalysis. Nature 2010 Jun 3; 465(7298): 584–9PubMedGoogle Scholar
  29. 29.
    Okamura K, Phillips MD, Tyler DM, et al. The regulatory activity of microRNA * species has substantial influence on microRNA and 3′ UTR evolution. Nat Struct Mol Biol 2008 Apr; 15(4): 354–63PubMedGoogle Scholar
  30. 30.
    Guo L, Lu Z. The fate of miRNA* strand through evolutionary analysis: implication for degradation as merely carrier strand or potential regulatory molecule? PLoS One. 2010 Jun 30; 5(6): e1 1387Google Scholar
  31. 31.
    Yang JS, Phillips MD, Betel D, et al. Widespread regulatory activity of vertebrate microRNA* species. RNA 2011 Feb; 17(2): 312–26PubMedGoogle Scholar
  32. 32.
    Iorio MV, Piovan C, Croce CM. Interplay between microRNAs and the epigenetic machinery: an intricate network. Biochim Biophys Acta 2010 Oct–Dec; 1799(10–12): 694–701PubMedGoogle Scholar
  33. 33.
    Tili E, Michaille JJ, Costinean S, et al. MicroRNAs, the immune system and rheumatic disease. Nat Clin Pract Rheumatol 2008 Oct; 4(10): 534–41PubMedGoogle Scholar
  34. 34.
    Furer V, Greenberg JD, Attur M, et al. The role of microRNA in rheumatoid arthritis and other autoimmune diseases. Clin Immunol 2010 Jul; 136(1): 1–15PubMedGoogle Scholar
  35. 35.
    Duroux-Richard I, Presumey J, Courties G, et al. MicroRNAs as new player in rheumatoid arthritis. Joint Bone Spine 2011 Jan; 78(1): 17–22PubMedGoogle Scholar
  36. 36.
    Wittmann J, Jäck HM. microRNAs in rheumatoid arthritis: midget RNAs with a giant impact. Ann Rheum Dis 2011 Mar; 70 Suppl. 1: 192–6Google Scholar
  37. 37.
    Nakasa T, Nagata Y, Yamasaki K, et al. A mini-review: microRNA in arthritis. Physiol Genomics 2011 May 1; 43(10): 566–70PubMedGoogle Scholar
  38. 38.
    Ceribelli A, Yao B, Dominguez-Gutierrez PR, et al. MicroRNAs in systemic rheumatic diseases. Arthritis Res Ther 2011 Jul 13; 13(4): 229PubMedGoogle Scholar
  39. 39.
    Ceribelli A, Nahid MA, Satoh M, et al. MicroRNAs in rheumatoid arthritis. FEBS Lett 2011 Dec 1; 585(23): 3667–74PubMedGoogle Scholar
  40. 40.
    Duroux-Richard I, Jorgensen C, Apparailly F. What do microRNAs mean for rheumatoid arthritis? Arthritis Rheum 2012 Jan; 64(1): 11–20PubMedGoogle Scholar
  41. 41.
    Baxter D, McInnes IB, Kurowska-Stolarska M. Novel regulatory mechanisms in inflammatory arthritis: a role for microRNA. Immunol Cell Biol 2012 Mar; 90(3): 288–92PubMedGoogle Scholar
  42. 42.
    Stanczyk J, Pedrioli DM, Brentano F, et al. Altered expression of MicroRNA in synovial fibroblasts and synovial tissue in rheumatoid arthritis. Arthritis Rheum 2008 Apr; 58(4): 1001–9PubMedGoogle Scholar
  43. 43.
    Kurowska-Stolarska M, Alivernini S, Ballantine LE, et al. MicroRNA-155as a proinflammatory regulator in clinical and experimental arthritis. Proc Natl Acad Sci U S A 2011 Jul 5; 108(27): 11193–8PubMedGoogle Scholar
  44. 44.
    Niimoto T, Nakasa T, Ishikawa M, et al. MicroRNA-146a expresses in interleukin-17 producing T cells in rheumatoid arthritis patients. BMC Musculoskelet Disord 2010 Sep 15; 11: 209PubMedGoogle Scholar
  45. 45.
    Pauley KM, Satoh M, Chan AL, et al. Upregulated miR-146a expression in peripheral blood mononuclear cells from rheumatoid arthritis patients. Arthritis Res Ther 2008; 10(4): R101PubMedGoogle Scholar
  46. 46.
    Blüml S, Bonelli M, Niederreiter B, et al. Essential role of micro RNA-155 in the pathogenesis of autoimmune arthritis in mice. Arthritis Rheum 2011 May; 63(5): 1281–8PubMedGoogle Scholar
  47. 47.
    Vigorito E, Perks KL, Abreu-Goodger C, et al. microRNA-155 regulates the generation of immunoglobulin class-switched plasma cells. Immunity 2007 Dec; 27(6): 847–59PubMedGoogle Scholar
  48. 48.
    O’Connell RM, Kahn D, Gibson WS, et al. MicroRNA-155 promotes autoimmune inflammation by enhancing inflammatory T cell development. Immunity 2010 Oct 29; 33(4): 607–19PubMedGoogle Scholar
  49. 49.
    Mizoguchi F, Izu Y, Hayata T, et al. Osteoclast-specific Dicer gene deficiency suppresses osteoclastic bone resorption. J Cell Biochem 2010 Apr 1; 109(5): 866–75PubMedGoogle Scholar
  50. 50.
    O’Connell RM, Rao DS, Chaudhuri AA, et al. Sustained expression of microRNA-155 in hematopoietic stem cells causes a myeloproliferative disorder. J Exp Med 2008 Mar 17; 205(3): 585–94PubMedGoogle Scholar
  51. 51.
    Tili E, Michaille JJ, Cimino A, et al. 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 2007 Oct 15; 179(8): 5082–9PubMedGoogle Scholar
  52. 52.
    Ceppi M, Pereira PM, Dunand-Sauthier I, et al. MicroRNA-155 modulates the interleukin-1 signaling pathway in activated human monocyte-derived dendritic cells. Proc Natl Acad Sci U S A 2009 Feb 24; 106(8): 2735–40PubMedGoogle Scholar
  53. 53.
    Ma X, Becker Buscaglia LE, Barker JR, et al. MicroRNAs in NF-kappaB signaling. J Mol Cell Biol 2011 Jun; 3(3): 159–66PubMedGoogle Scholar
  54. 54.
    Nakasa T, Miyaki S, Okubo A, et al. Expression of microRNA-146 in rheumatoid arthritis synovial tissue. Arthritis Rheum 2008 May; 58(5): 1284–92PubMedGoogle Scholar
  55. 55.
    Li J, Wan Y, Guo Q, et al. Altered microRNA expression profile with miR-146a upregulation in CD4+ T cells from patients with rheumatoid arthritis. Arthritis Res Ther 2010; 12(3): R81PubMedGoogle Scholar
  56. 56.
    Taganov KD, Boldin MP, Chang KJ, et al. NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci U S A 2006 Aug 15; 103(33): 12481–6PubMedGoogle Scholar
  57. 57.
    Yamasaki K, Nakasa T, Miyaki S, et al. Expression of MicroRNA-146a in osteoarthritis cartilage. Arthritis Rheum 2009 Apr; 60(4): 1035–41PubMedGoogle Scholar
  58. 58.
    Curtale G, Citarella F, Carissimi C, et al. An emerging player in the adaptive immune response: microRNA-146a is a modulator of IL-2 expression and activation-induced cell death in T lymphocytes. Blood 2010 Jan 14; 115(2): 265–73PubMedGoogle Scholar
  59. 59.
    Pap T, Franz JK, Hummel KM, et al. Activation of synovial fibroblasts in rheumatoid arthritis: lack of expression of the tumour suppressor PTEN at sites of invasive growth and destruction. Arthritis Res 2000; 2(1): 59–64PubMedGoogle Scholar
  60. 60.
    Salmon M, Scheel-Toellner D, Huissoon AP, et al. Inhibition of T cell apoptosis in the rheumatoid synovium. J Clin Invest 1997 Feb 1; 99(3): 439–46PubMedGoogle Scholar
  61. 61.
    Cantwell MJ, Hua T, Zvaifler NJ, et al. Deficient Fas ligand expression by synovial lymphocytes from patients with rheumatoid arthritis. Arthritis Rheum 1997 Sep; 40(9): 1644–52PubMedGoogle Scholar
  62. 62.
    Nakasa T, Shibuya H, Nagata Y, et al. The inhibitory effect of microRNA-146a expression on bone destruction in collagen-induced arthritis. Arthritis Rheum 2011 Jun; 63(6): 1582–90PubMedGoogle Scholar
  63. 63.
    Stanczyk J, Ospelt C, Karouzakis E, et al. Altered expression of miR-203 in rheumatoid arthritis synovial fibroblasts and its role in fibroblast activation. Arthritis Rheum 2011 Feb; 63(2): 373–81PubMedGoogle Scholar
  64. 64.
    Yu H, Lu J, Zuo L, et al. Epstein-Barr virus downregulates microRNA-203 through the oncoprotein latent membrane protein 1: a contribution to increased tumor incidence in epithelial cells. J Virol 2012 Mar; 86(6): 3088–99PubMedGoogle Scholar
  65. 65.
    Ru P, Steele R, Hsueh EC, et al. Anti-miR-203 upregulates SOCS3 expression in breast cancer cells and enhances cisplatin chemosensitivity. Genes Cancer 2011 Jul; 2(7): 720–7PubMedGoogle Scholar
  66. 66.
    Bueno MJ, Pérez de Castro I, Gómez de Cedrón M, et al. Genetic and epigenetic silencing of microRNA-203 enhances ABL1 and BCR-ABL1 oncogene expression. Cancer Cell 2008 Jun; 13(6): 496–506PubMedGoogle Scholar
  67. 67.
    Furuta M, Kozaki KI, Tanaka S, et al. miR-124 and miR-203 are epigenetically silenced tumor-suppressive microRNAs in hepatocellular carcinoma. Carcinogenesis 2010 May; 31(5): 766–76PubMedGoogle Scholar
  68. 68.
    Viticchiè G, Lena AM, Latina A, et al. MiR-203 controls proliferation, migration and invasive potential of prostate cancer cell lines. Cell Cycle 2011 Apr 1; 10(7): 1121–31PubMedGoogle Scholar
  69. 69.
    Greither T, Grochola LF, Udelnow A, et al. Elevated expression of microRNAs 155, 203, 210 and 222 in pancreatic tumors is associated with poorer survival. Int J Cancer 2010 Jan 1; 126(1): 73–80PubMedGoogle Scholar
  70. 70.
    Nakamachi Y, Kawano S, Takenokuchi M, et al. MicroRNA-124a is a key regulator of proliferation and monocyte chemoattractant protein 1 secretion in fibroblast-like synoviocytes from patients with rheumatoid arthritis. Arthritis Rheum 2009 May; 60(5): 1294–304PubMedGoogle Scholar
  71. 71.
    Koch AE, Kunkel SL, Harlow LA, et al. Enhanced production of monocyte chemoattractant protein 1 in rheumatoid arthritis. J Clin Invest 1992 Sep; 90(3): 772–9PubMedGoogle Scholar
  72. 72.
    Koch AE, Harlow LA, Haines GK, et al. Vascular endothelial growth factor: a cytokine modulating endothelial function in rheumatoid arthritis. J Immunol 1994 Apr 15; 152(8): 4149–56PubMedGoogle Scholar
  73. 73.
    Akhavani MA, Madden L, Buysschaert I, et al. Hypoxia upregulates angiogenesis and synovial cell migration in rheumatoid arthritis. Arthritis Res Ther 2009; 11(3): R64PubMedGoogle Scholar
  74. 74.
    Kawano S, Nakamachi Y. miR-124a as a key regulator of proliferation and MCP-1 secretion in synoviocytes from patients with rheumatoid arthritis. Ann Rheum Dis 2011 Mar; 70 Suppl. 1: 188–91Google Scholar
  75. 75.
    Lujambio A, Ropero S, Ballestar E, et al. Genetic unmasking of an epigenetically silenced microRNA in human cancer cells. Cancer Res 2007 Feb 15; 67(4): 1424–9PubMedGoogle Scholar
  76. 76.
    Fulci V, Scappucci G, Sebastiani GD, et al. miR-223 is overexpressed in T-lymphocytes of patients affected by rheumatoid arthritis. Hum Immunol 2010 Feb; 71(2): 206–11PubMedGoogle Scholar
  77. 77.
    Nagata Y, Nakasa T, Mochizuki Y, et al. Induction of apoptosis in the synovium of mice with autoantibody-mediated arthritis by the intraarticular injection of double-stranded MicroRNA-15a. Arthritis Rheum 2009 Sep; 60(9): 2677–83PubMedGoogle Scholar
  78. 78.
    Cimmino A, Calin GA, Fabbri M, et al. miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci U S A 2005 Sep 27; 102(39): 13944–9PubMedGoogle Scholar
  79. 79.
    Alsaleh G, Suffert G, Semaan N, et al. Bruton’s tyrosine kinase is involved in miR-346-related regulation of IL-18 release by lipopolysaccharide-activated rheumatoid fibroblast-like synoviocytes. J Immunol 2009 Apr 15; 182(8): 5088–97PubMedGoogle Scholar
  80. 80.
    Horwood NJ, Mahon T, McDaid JP, et al. Epigenetic control in rheumatoid arthritis synovial fibroblasts. Bruton’s tyrosine kinase is required for lipopolysaccharide-induced tumor necrosis factor alpha production. J Exp Med 2003 Jun 16; 197(12): 1603–11PubMedGoogle Scholar
  81. 81.
    Semaan N, Frenzel L, Alsaleh G, et al. miR-346 controls release of TNF-α protein and stability of its mRNA in rheumatoid arthritis via tristetraprolin stabilization. PLoS ONE 2011; 6(5): e19827PubMedGoogle Scholar
  82. 82.
    Niederer F, Trenkmann M, Ospelt C, et al. Downregulation of microRNA-34a* in rheumatoid arthritis synovial fibroblasts promotes apoptosis resistance. Arthritis Rheum Epub 2011 Dec 12Google Scholar
  83. 83.
    Iliopoulos D, Malizos KN, Oikonomou P, et al. Integrative microRNA and proteomic approaches identify novel osteoarthritis genes and their collaborative metabolic and inflammatory networks. PLoS ONE 2008; 3(11): e3740PubMedGoogle Scholar
  84. 84.
    Jones SW, Watkins G, Le Good N, et al. The identification of differentially expressed microRNA in osteoarthritic tissue that modulate the production of TNF-alpha and MMP13. Osteoarthritis Cartilage 2009 Apr; 17(4): 464–72PubMedGoogle Scholar
  85. 85.
    Abouheif MM, Nakasa T, Shibuya H, et al. Silencing microRNA-34a inhibits chondrocyte apoptosis in a rat osteoarthritis model in vitro. Rheumatology (Oxford) 2010 Nov; 49(11): 2054–60Google Scholar
  86. 86.
    Miyaki S, Nakasa T, Otsuki S, et al. MicroRNA-140 is expressed in differ-entiated human articular chondrocytes and modulates interleukin-1 responses. Arthritis Rheum 2009 Sep; 60(9): 2723–30PubMedGoogle Scholar
  87. 87.
    Miyaki S, Sato T, Inoue A, et al. MicroRNA-140 plays dual roles in both cartilage development and homeostasis. Genes Dev 2010 Jun 1; 24(11): 1173–85PubMedGoogle Scholar
  88. 88.
    Tardif G, Hum D, Pelletier JP, et al. Regulation of the IGFBP-5 and MMP-13 genes by the microRNAs miR-140 and miR-27a in human osteoarthritic chondrocytes. BMC Musculoskelet Disord 2009 Nov 30; 10: 148PubMedGoogle Scholar
  89. 89.
    Liang Y, Ridzon D, Wong L, et al. Characterization of microRNA expression profiles in normal human tissues. BMC Genomics 2007 Jun 12; 8: 166PubMedGoogle Scholar
  90. 90.
    Gaur A, Jewell DA, Liang Y, et al. Characterization of microRNA expression levels and their biological correlates in human cancer cell lines. Cancer Res 2007 Mar 15; 67(6): 2456–68PubMedGoogle Scholar
  91. 91.
    Zen K, Zhang CY. Circulating MicroRNAs: a novel class of biomarkers to diagnose and monitor human cancers. Med Res Rev 2012 Mar; 32(2): 326–48PubMedGoogle Scholar
  92. 92.
    Mitchell PS, Parkin RK, Kroh EM, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A 2008 Jul 29; 105(30): 10513–8PubMedGoogle Scholar
  93. 93.
    Hunter MP, Ismail N, Zhang X, et al. Detection of microRNA expression in human peripheral blood microvesicles. PLoS ONE 2008; 3(11): e3694PubMedGoogle Scholar
  94. 94.
    Iguchi H, Kosaka N, Ochiya T. Secretory microRNAs as a versatile communication tool. Commun Integr Biol 2010 Sep; 3(5): 478–81PubMedGoogle Scholar
  95. 95.
    Kosaka N, Iguchi H, Yoshioka Y, et al. Secretory mechanisms and intercellular transfer of microRNAs in living cells. J Biol Chem 2010 Jun 4; 285(23): 17442–52PubMedGoogle Scholar
  96. 96.
    Valadi H, Ekström K, Bossios A, et al. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 2007 Jun; 9(6): 654–9PubMedGoogle Scholar
  97. 97.
    Arroyo JD, Chevillet JR, Kroh EM, et al. Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma. Proc Natl Acad Sci U S A 2011 Mar 22; 108(12): 5003–8PubMedGoogle Scholar
  98. 98.
    Vickers KC, Palmisano BT, Shoucri BM, et al. MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins. Nat Cell Biol 2011 Apr; 13(4): 423–33PubMedGoogle Scholar
  99. 99.
    Wang K, Zhang S, Weber J, et al. Export of microRNAs and microRNA-protective protein by mammalian cells. Nucleic Acids Res 2010 Nov; 38(20): 7248–59PubMedGoogle Scholar
  100. 100.
    Gilad S, Meiri E, Yogev Y, et al. Serum microRNAs are promising novel biomarkers. PLoS ONE 2008 Sep 5; 3(9): e3148PubMedGoogle Scholar
  101. 101.
    Pigati L, Yaddanapudi SC, Iyengar R, et al. Selective release of microRNA species from normal and malignant mammary epithelial cells. PLoS ONE 2010 Oct 20; 5(10):e13515PubMedGoogle Scholar
  102. 102.
    Chen X, Ba Y, Ma L, et al. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res 2008 Oct; 18(10): 997–1006PubMedGoogle Scholar
  103. 103.
    Wang JF, Yu ML, Yu G, et al. Serum miR-146a and miR-223 as potential new biomarkers for sepsis. Biochem Biophys Res Commun 2010 Mar 26; 394(1): 184–8PubMedGoogle Scholar
  104. 104.
    Murata K, Yoshitomi H, Tanida S, et al. Plasma and synovial fluid microRNAs as potential biomarkers of rheumatoid arthritis and osteoarthritis. Arthritis Res Ther 2010; 12(3): R86PubMedGoogle Scholar
  105. 105.
    Alevizos I, Illei GG. MicroRNAs as biomarkers in rheumatic diseases. Nat Rev Rheumatol 2010 Jul; 6(7): 391–8PubMedGoogle Scholar
  106. 106.
    Smolen JS, Aletaha D, Koeller M, et al. New therapies for treatment of rheumatoid arthritis. Lancet 2007 Dec 1; 370(9602): 1861–74PubMedGoogle Scholar
  107. 107.
    Senolt L, Vencovský J, Pavelka K, et al. Prospective new biological therapies for rheumatoid arthritis. Autoimmun Rev 2009 Dec; 9(2): 102–7PubMedGoogle Scholar
  108. 108.
    Wang V, Wu W. MicroRNA-based therapeutics for cancer. BioDrugs 2009; 23(1): 15–23PubMedGoogle Scholar
  109. 109.
    McDermott AM, Heneghan HM, Miller N, et al. The therapeutic potential of microRNAs: disease modulators and drug targets. Pharm Res 2011 Dec; 28(12): 3016–29PubMedGoogle Scholar
  110. 110.
    Kim M, Kasinski AL, Slack FJ. MicroRNA therapeutics in preclinical cancer models. Lancet Oncol 2011 Apr; 12(4): 319–21PubMedGoogle Scholar
  111. 111.
    Nana-Sinkam SP, Croce CM. MicroRNAs as therapeutic targets in cancer. Transl Res 2011 Apr; 157(4): 216–25PubMedGoogle Scholar
  112. 112.
    Rossbach M. Small non-coding RNAs as novel therapeutics. Curr Mol Med 2010 Jun; 10(4): 361–8PubMedGoogle Scholar
  113. 113.
    Weiler J, Hunziker J, Hall J. Anti-miRNA oligonucleotides (AMOs): ammunition to target miRNAs implicated in human disease? Gene Ther 2006 Mar; 13(6): 496–502PubMedGoogle Scholar
  114. 114.
    Wahlestedt C, Salmi P, Good L, et al. Potent and nontoxic antisense oligonucleotides containing locked nucleic acids. Proc Natl Acad Sci U S A 2000 May 9; 97(10): 5633–8PubMedGoogle Scholar
  115. 115.
    Krützfeldt J, Rajewsky N, Braich R, et al. Silencing of microRNAs in vivo with ‘antagomir’. Nature 2005 Dec 1; 438(7068): 685–9PubMedGoogle Scholar
  116. 116.
    Lanford RE, Hildebrandt-Eriksen ES, Petri A, et al. Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection. Science 2010 Jan 8; 327(5962): 198–201PubMedGoogle Scholar
  117. 117.
    Santaris Pharma A/S. Multiple ascending dose study of miravirsen in treatment-naïve chronic hepatitis C subjects [ClinicalTrials.gov identifier NCT01200420]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2012 Mar 20]
  118. 118.
    Ebert MS, Neilson JR, Sharp PA. MicroRNA sponges: competitive inhibitors of small RNAs in mammalian cells. Nat Methods 2007 Sep; 4(9): 721–6PubMedGoogle Scholar
  119. 119.
    Wang Z. The principles of MiRNA-masking antisense oligonucleotides technology. Methods Mol Biol 2011; 676: 43–9PubMedGoogle Scholar
  120. 120.
    Ma L, Young J, Prabhala H, et al. miR-9, a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis. Nat Cell Biol 2010 Mar; 12(3): 247–56PubMedGoogle Scholar
  121. 121.
    Choi WY, Giraldez AJ, Schier AF. Target protectors reveal dampening and balancing of Nodal agonist and antagonist by miR-430. Science 2007 Oct 12; 318(5848): 271–4PubMedGoogle Scholar
  122. 122.
    Li C, Feng Y, Coukos G, et al. Therapeutic micro RNA strategies in human cancer. AAPS J 2009 Dec; 11(4): 747–57PubMedGoogle Scholar
  123. 123.
    Chen Y, Zhu X, Zhang X, et al. Nanoparticles modified with tumor-targeting scFv deliver siRNA and miRNA for cancer therapy. Mol Ther 2010 Sep; 18(9): 1650–6PubMedGoogle Scholar
  124. 124.
    Wolfrum C, Shi S, Jayaprakash KN, et al. Mechanisms and optimization of in vivo delivery of lipophilic siRNAs. Nat Biotechnol 2007 Oct; 25(10): 1149–57PubMedGoogle Scholar
  125. 125.
    Simeoni F, Morris MC, Heitz F, et al. Insight into the mechanism of the peptide-based gene delivery system MPG: implications for delivery of siRNA into mammalian cells. Nucleic Acids Res 2003 Jun 1; 31(11): 2717–24PubMedGoogle Scholar
  126. 126.
    Minakuchi Y, Takeshita F, Kosaka N, et al. Atelocollagen-mediated synthetic small interfering RNA delivery for effective gene silencing in vitro and in vivo. Nucleic Acids Res 2004 Jul 22; 32(13): e109PubMedGoogle Scholar
  127. 127.
    Grimm D, Streetz KL, Jopling CL, et al. Fatality in mice due to oversaturation of cellular micro RNA/short hairpin RNA pathways. Nature 2006 May 25; 441(7092): 537–41PubMedGoogle Scholar
  128. 128.
    Kota J, Chivukula RR, O’Donnell KA, et al. Therapeutic microRNA delivery suppresses tumorigenesis in a murine liver cancer model. Cell 2009 Jun 12; 137(6): 1005–17PubMedGoogle Scholar
  129. 129.
    Nasser MW, Datta J, Nuovo G, et al. Down-regulation of micro-RNA-1 (miR-1) in lung cancer. Suppression of tumorigenic property of lung cancer cells and their sensitization to doxorubicin-induced apoptosis by miR-1. J Biol Chem 2008 Nov 28; 283(48): 33394–405PubMedGoogle Scholar
  130. 130.
    Kong W, He L, Coppola M, et al. MicroRNA-155 regulates cell survival, growth, and chemosensitivity by targeting FOXO3a in breast cancer. J Biol Chem 2010 Jun 4; 285(23): 17869–79PubMedGoogle Scholar
  131. 131.
    Ferracin M, Zagatti B, Rizzotto L, et al. MicroRNAs involvement in fludara-bine refractory chronic lymphocytic leukemia. Mol Cancer 2010 May 26; 9:123PubMedGoogle Scholar
  132. 132.
    Blower PE, Chung JH, Verducci JS, et al. MicroRNAs modulate the chemosensitivity of tumor cells. Mol Cancer Ther 2008 Jan; 7(1): 1–9PubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2012

Authors and Affiliations

  • Mária Filková
    • 1
    Email author
  • Astrid Jüngel
    • 1
  • Renate E. Gay
    • 1
  • Steffen Gay
    • 1
  1. 1.Center of Experimental RheumatologyUniversity Hospital ZurichZurichSwitzerland

Personalised recommendations