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Review article: Biomedical intelligence

Vol. 141 No. 1112 (2011)

miRNAs and rheumatoid arthritis – promising novel biomarkers

  • I Duroux-Richard
  • C Jorgensen
  • F Apparailly
DOI
https://doi.org/10.4414/smw.2011.13175
Cite this as:
Swiss Med Wkly. 2011;141:w13175
Published
14.03.2011

Summary

Biomarkers are indicators of biological conditions that can be detected and measured in body fluids or tissues. Biomarkers can be detectable before the clinical onset of the disease, and are thus useful for prognosis; they can be measured at early stages of the disease and are useful for stratification and classification of the disease and patients; they can be monitored along the disease course and used as indicators of risk factors and pharmacological response to treatment. Ideally, biomarkers should be sensitive, specific, have high predictive power, and be easily accessible. Rheumatoid arthritis (RA) is the most frequent chronic inflammatory disorder, affecting millions of people worldwide and leading to joint damage and substantial morbidity. RA is a heterogeneous disorder with a fluctuating clinical course and unpredictable prognosis. And although a large panel of biologics is available to clinicians, the main challenge remains to treat patients as early as possible with the most personalised therapy. Today, the most challenging issue in RA is the identification of biomarkers for early disease diagnosis and for prediction of drug response. Among molecules that can fulfil this expectation, micro(mi)-RNAs certainly represent an option. The potential value of miRNAs as a novel class of biomarkers is well documented in cancer. Moreover, the presence and stability of miRNAs in body fluids provide fingerprints that can serve as molecular biomarkers for disease diagnosis and therapeutic outcome. As a growing body of evidences reveals abnormal expression of specific miRNAs in RA tissues, the use of a blood-based miRNA signature for optimal diagnosis and treatment becomes a realistic option.

References

  1. van der Heijde DM, van Leeuwen MA, van Riel PL, Koster AM, van ’t Hof MA, van Rijswijk MH, et al. Biannual radiographic assessments of hands and feet in a three-year prospective followup of patients with early rheumatoid arthritis. Arthritis Rheum. 1992;35(1):26–34.
  2. Pincus T. The underestimated long term medical and economic consequences of rheumatoid arthritis. Drugs. 1995;50(Suppl 1):1–14.
  3. van der Kooij SM, de Vries-Bouwstra JK, Goekoop-Ruiterman YP, van Zeben D, Kerstens PJ, Gerards AH, et al. Limited efficacy of conventional DMARDs after initial methotrexate failure in patients with recent onset rheumatoid arthritis treated according to the disease activity score. Ann Rheum Dis. 2007;66(10):1356–62.
  4. Kirwan J. Adverse effects of low-dose glucocorticoids and DMARD therapy in patients with RA – a complex relationship? Nat Clin Pract Rheumatol. 2008;4(11):568–9.
  5. Feldmann M, Williams RO, Paleolog E. What have we learnt from targeted anti-TNF therapy? Ann Rheum Dis. 2011;69(Suppl 1):i97–9.
  6. McInnes IB, Schett G. Cytokines in the pathogenesis of rheumatoid arthritis. Nat Rev Immunol. 2007;7(6):429–42.
  7. Genovese MC, Bathon JM, Fleischmann RM, Moreland LW, Martin RW, Whitmore JB, et al. Longterm safety, efficacy, and radiographic outcome with etanercept treatment in patients with early rheumatoid arthritis. J Rheumatol. 2005;32(7):1232–42.
  8. Bongartz T, Sutton AJ, Sweeting MJ, Buchan I, Matteson EL, Montori V. Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials. Jama. 2006;295(19):2275–85.
  9. Genevay S, Finckh A, Ciurea A, Chamot AM, Kyburz D, Gabay C. Tolerance and effectiveness of anti-tumor necrosis factor alpha therapies in elderly patients with rheumatoid arthritis: a population-based cohort study. Arthritis Rheum. 2007;57(4):679–85.
  10. Simard JF, Arkema EV, Sundstrom A, Geborek P, Saxne T, Baecklund E, et al. Ten years with biologics: to whom do data on effectiveness and safety apply? Rheumatology. (Oxford) 2011;50(1):204–13.
  11. Gabriel SE. Tumor necrosis factor inhibition: a part of the solution or a part of the problem of heart failure in rheumatoid arthritis? Arthritis Rheum. 2008;58(3):637–40.
  12. Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T. Identification of novel genes coding for small expressed RNAs. Science. 2001;294(5543):853–8.
  13. Lee Y, Jeon K, Lee JT, Kim S, Kim VN. MicroRNA maturation: stepwise processing and subcellular localization. Embo J. 2002;21(17):4663–70.
  14. Lee Y, Ahn C, Han J, Choi H, Kim J, Yim J, et al. The nuclear RNase III Drosha initiates microRNA processing. Nature. 2003;425(6956):415–9.
  15. Yi R, Qin Y, Macara IG, Cullen BR. Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs. Genes Dev. 2003;17(24):3011–6.
  16. Du T, Zamore PD. microPrimer: the biogenesis and function of microRNA. Development. 2005;132(21):4645–52.
  17. Hammond SM, Bernstein E, Beach D, Hannon GJ. An RNA-directed nuclease mediates post-transcriptional gene silencing in Drosophila cells. Nature. 2000;404(6775):293–6.
  18. Chi SW, Zang JB, Mele A, Darnell RB. Argonaute HITS-CLIP decodes microRNA-mRNA interaction maps. Nature. 2009;460(7254):479–86.
  19. Meister G, Landthaler M, Peters L, Chen PY, Urlaub H, Luhrmann R, et al. Identification of novel argonaute-associated proteins. Curr Biol. 2005;15(23):2149–55.
  20. Orom UA, Nielsen FC, Lund AH. MicroRNA-10a binds the 5‘UTR of ribosomal protein mRNAs and enhances their translation. Mol Cell. 2008;30(4):460–71.
  21. 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. U S A 2007;104(23):9667–72.
  22. Zhou X, Duan X, Qian J, Li F. Abundant conserved microRNA target sites in the 5‘-untranslated region and coding sequence. Genetica. 2009;137(2):159–64.
  23. Winter J, Jung S, Keller S, Gregory RI, Diederichs S. Many roads to maturity: microRNA biogenesis pathways and their regulation. Nat Cell Biol. 2009;11(3):228–34.
  24. Ambros V. The functions of animal microRNAs. Nature. 2004;431(7006):350–5.
  25. Liang Y, Ridzon D, Wong L, Chen C. Characterization of microRNA expression profiles in normal human tissues. BMC Genomics. 2007;8:166.
  26. Soifer HS, Rossi JJ, Saetrom P. MicroRNAs in disease and potential therapeutic applications. Mol Ther. 2007;15(12):2070–9.
  27. Bhanji RA, Eystathioy T, Chan EK, Bloch DB, Fritzler MJ. Clinical and serological features of patients with autoantibodies to GW/P bodies. Clin Immunol. 2007;125(3):247–56.
  28. Pauley KM, Satoh M, Chan AL, Bubb MR, Reeves WH, Chan EK. Upregulated miR-146a expression in peripheral blood mononuclear cells from rheumatoid arthritis patients. Arthritis Res Ther. 2008;10(4):R101.
  29. Nakasa T, Miyaki S, Okubo A, Hashimoto M, Nishida K, Ochi M, et al. Expression of microRNA-146 in rheumatoid arthritis synovial tissue. Arthritis Rheum. 2008;58(5):1284–92.
  30. Stanczyk J, Pedrioli DM, Brentano F, Sanchez-Pernaute O, Kolling C, Gay RE, et al. Altered expression of MicroRNA in synovial fibroblasts and synovial tissue in rheumatoid arthritis. Arthritis Rheum. 2008;58(4):1001–9.
  31. Alsaleh G, Suffert G, Semaan N, Juncker T, Frenzel L, Gottenberg JE, 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;182(8):5088–97.
  32. Fulci V, Scappucci G, Sebastiani GD, Giannitti C, Franceschini D, Meloni F, et al. miR-223 is overexpressed in T-lymphocytes of patients affected by rheumatoid arthritis. Hum Immunol. 2010;71(2):206–11.
  33. Li J, Wan Y, Guo Q, Zou L, Zhang J, Fang Y, et al. Altered micro- RNA expression profile with miR-146a upregulation in CD4+ T cells from patients with rheumatoid arthritis. Arthritis Res Ther. 2010;12(3):R81.
  34. Murata K, Yoshitomi H, Tanida S, Ishikawa M, Nishitani K, Ito H, et al. Plasma and synovial fluid microRNAs as potential biomarkers of rheumatoid arthritis and osteoarthritis. Arthritis Res Ther. 2010;12(3):R86.
  35. Nakamachi Y, Kawano S, Takenokuchi M, Nishimura K, Sakai Y, Chin T, 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;60(5):1294–304.
  36. Niimoto T, Nakasa T, Ishikawa M, Okuhara A, Izumi B, Deie M, et al. MicroRNA-146a expresses in interleukin-17 producing T cells in rheumatoid arthritis patients. BMC Musculoskelet Disord. 2010;11:209.
  37. Stanczyk J, Ospelt C, Karouzakis E, Filer A, Raza K, Kolling C, et al. Altered expression of miR-203 in rheumatoid arthritis synovial fibroblasts and its role in fibroblast activation. Arthritis Rheum. 2011;63(2):373–81.
  38. Lagos D, Pollara G, Henderson S, Gratrix F, Fabani M, Milne RS, et al. miR-132 regulates antiviral innate immunity through suppression of the p300 transcriptional co-activator. Nat Cell Biol. 2010;12(5):513-9.
  39. Wang JF, Yu ML, Yu G, Bian JJ, Deng XM, Wan XJ, et al. Serum miR-146a and miR-223 as potential new biomarkers for sepsis. Biochem Biophys Res Commun. 2010;394(1):184–8.
  40. Pulikkan JA, Dengler V, Peramangalam PS, Peer Zada AA, Muller-Tidow C, Bohlander SK, et al. Cell-cycle regulator E2F1 and microRNA-223 comprise an autoregulatory negative feedback loop in acute myeloid leukemia. Blood. 2010;115(9):1768–78.
  41. Carissimi C, Fulci V, Macino G. MicroRNAs: Novel regulators of immunity. Autoimmun Rev 2009;8(6):520–4.
  42. Duroux-Richard I, Presumey J, Courties G, Gay S, Gordeladze JO, Jorgensen C, et al. microRNAs as new player in rheumatoid arthritis. Join Bone Spine. 2011;78(1):17–22.
  43. Taganov KD, Boldin MP, Chang KJ, Baltimore D. 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;103(33):12481–6.
  44. Chen X, Ba Y, Ma L, Cai X, Yin Y, Wang K, et al. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res. 2008;18(10):997–1006.
  45. Gilad S, Meiri E, Yogev Y, Benjamin S, Lebanony D, Yerushalmi N, et al. Serum microRNAs are promising novel biomarkers. PLoS ONE. 2008;3(9):e3148.
  46. Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci. U S A 2008;105(30):10513–8.
  47. White MA, Fatoohi E, Metias M, Jung K, Stephan C, Yousef GM. Metastamirs: a stepping stone towards improved cancer management. Nature Reviews Clinical Oncology. 2010;173.
  48. Mraz M, Malinova K, Mayer J, Pospisilova S. MicroRNA isolation and stability in stored RNA samples. Biochem Biophys Res Commun. 2009;390(1):1–4.
  49. Hunter MP, Ismail N, Zhang X, Aguda BD, Lee EJ, Yu L, et al. Detection of microRNA expression in human peripheral blood microvesicles. PLoS ONE. 2008;3(11):e3694.
  50. Oliviero F, Ramonda R, Punzi L. New horizons in osteoarthritis. Swiss Med Wkly. 2010;140:w13098.