Skip to main content
SpringerLink
Log in

MicroRNAs in Systemic Lupus Erythematosus: a Perspective on the Path from Biological Discoveries to Clinical Practice

  • Systemic Lupus Erythematosus (G Tsokos, Section Editor)
  • Published:
Current Rheumatology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

MicroRNAs (miRNAs) play essential roles in immune abnormalities and organ damage of systemic lupus erythematosus (SLE). Current findings have indicated potential clinical applications of miRNAs for combating SLE. Here, we review recent evidence which support the notions that miRNAs can be novel biomarkers and therapeutic agents for SLE.

Recent Findings

Following years of the studies of the expression patterns of miRNAs in both peripheral blood cells and body fluids, such as plasma and urine, several miRNAs or miRNA combinations have been associated with disease activity and specific organ damage. In depth analysis reveals complex and multiple roles of certain miRNAs in the pathogenesis of SLE. Manipulating miRNA expression shows in vivo therapeutic effects in lupus mouse models.

Summary

MiRNAs contribute to the immune disorders and organ damage in SLE. MiRNA based biomarkers and therapies have the potential to be viable options for the treatment of SLE.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. D'Cruz DP, Khamashta MA, Hughes GR. Systemic lupus erythematosus. Lancet. 2007;369(9561):587–96. https://doi.org/10.1016/s0140-6736(07)60279-7.

    Article  PubMed  Google Scholar 

  2. Dorner T, Furie R. Novel paradigms in systemic lupus erythematosus. Lancet. 2019;393(10188):2344–58. https://doi.org/10.1016/s0140-6736(19)30546-x.

    Article  PubMed  Google Scholar 

  3. Lewis MJ, Jawad AS. The effect of ethnicity and genetic ancestry on the epidemiology, clinical features and outcome of systemic lupus erythematosus. Rheumatology (Oxford). 2017;56(suppl_1):i67–77. https://doi.org/10.1093/rheumatology/kew399.

    Article  CAS  Google Scholar 

  4. Costenbader KH, Feskanich D, Stampfer MJ, Karlson EW. Reproductive and menopausal factors and risk of systemic lupus erythematosus in women. Arthritis Rheum. 2007;56(4):1251–62. https://doi.org/10.1002/art.22510.

    Article  PubMed  Google Scholar 

  5. Chakravarty EF, Bush TM, Manzi S, Clarke AE, Ward MM. Prevalence of adult systemic lupus erythematosus in California and Pennsylvania in 2000: estimates obtained using hospitalization data. Arthritis Rheum. 2007;56(6):2092–4. https://doi.org/10.1002/art.22641.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Rullo OJ, Tsao BP. Recent insights into the genetic basis of systemic lupus erythematosus. Ann Rheum Dis. 2013;72(suppl 2):ii56–61. https://doi.org/10.1136/annrheumdis-2012-202351.

    Article  CAS  PubMed  Google Scholar 

  7. Tsokos GC, Lo MS, Costa Reis P, Sullivan KE. New insights into the immunopathogenesis of systemic lupus erythematosus. Nat Rev Rheumatol. 2016;12(12):716–30. https://doi.org/10.1038/nrrheum.2016.186.

    Article  CAS  PubMed  Google Scholar 

  8. Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993;75(5):843–54. https://doi.org/10.1016/0092-8674(93)90529-y.

    Article  CAS  PubMed  Google Scholar 

  9. Reinhart BJ, Slack FJ, Basson M, Pasquinelli AE, Bettinger JC, Rougvie AE, et al. The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature. 2000;403(6772):901–6. https://doi.org/10.1038/35002607.

    Article  CAS  Google Scholar 

  10. Kozomara A, Griffiths-Jones S. miRBase: annotating high confidence microRNAs using deep sequencing data. Nucleic Acids Res. 2014;42(D1):D68–73. https://doi.org/10.1093/nar/gkt1181.

    Article  CAS  PubMed  Google Scholar 

  11. Bartel DP. Metazoan MicroRNAs. Cell. 2018;173(1):20–51. https://doi.org/10.1016/j.cell.2018.03.006.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Xiao C, Rajewsky K. MicroRNA control in the immune system: basic principles. Cell. 2009;136(1):26–36. https://doi.org/10.1016/j.cell.2008.12.027.

    Article  CAS  PubMed  Google Scholar 

  13. Croce CM. Causes and consequences of microRNA dysregulation in cancer. Nat Rev Genet. 2009;10(10):704–14. https://doi.org/10.1038/nrg2634.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Condorelli G, Latronico MV, Cavarretta E. microRNAs in cardiovascular diseases: current knowledge and the road ahead. J Am Coll Cardiol. 2014;63(21):2177–87. https://doi.org/10.1016/j.jacc.2014.01.050.

    Article  CAS  PubMed  Google Scholar 

  15. Pauley KM, Cha S, Chan EKL. MicroRNA in autoimmunity and autoimmune diseases. J Autoimmun. 2009;32(3–4):189–94. https://doi.org/10.1016/j.jaut.2009.02.012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. 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. https://doi.org/10.1016/j.clim.2007.07.016.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Jakymiw A, Ikeda K, Fritzler MJ, Reeves WH, Satoh M, Chan EK. Autoimmune targeting of key components of RNA interference. Arthritis Res Ther. 2006;8(4):R87. https://doi.org/10.1186/ar1959.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Dai Y, Huang YS, Tang M, Lv TY, Hu CX, Tan YH, et al. Microarray analysis of microRNA expression in peripheral blood cells of systemic lupus erythematosus patients. Lupus. 2007;16(12):939–46. https://doi.org/10.1177/0961203307084158.

    Article  CAS  PubMed  Google Scholar 

  19. Dai R, Zhang Y, Khan D, Heid B, Caudell D, Crasta O, et al. Identification of a common lupus disease-associated microRNA expression pattern in three different murine models of lupus. PLoS One. 2010;5(12):e14302. https://doi.org/10.1371/journal.pone.0014302.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Qu B, Shen N. miRNAs in the pathogenesis of systemic lupus Erythematosus. Int J Mol Sci. 2015;16(5):9557–72. https://doi.org/10.3390/ijms16059557.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Wang J, Chen J, Sen S. MicroRNA as biomarkers and diagnostics. J Cell Physiol. 2016;231(1):25–30. https://doi.org/10.1002/jcp.25056.

    Article  CAS  PubMed  Google Scholar 

  22. Weber JA, Baxter DH, Zhang S, Huang DY, Huang KH, Lee MJ, et al. The microRNA spectrum in 12 body fluids. Clin Chem. 2010;56(11):1733–41. https://doi.org/10.1373/clinchem.2010.147405.

    Article  CAS  Google Scholar 

  23. Long H, Wang X, Chen Y, Wang L, Zhao M, Lu Q. Dysregulation of microRNAs in autoimmune diseases: pathogenesis, biomarkers and potential therapeutic targets. Cancer Lett. 2018;428:90–103. https://doi.org/10.1016/j.canlet.2018.04.016.

    Article  CAS  PubMed  Google Scholar 

  24. Greenwood DL, Gitlits VM, Alderuccio F, Sentry JW, Toh BH. Autoantibodies in neuropsychiatric lupus. Autoimmunity. 2002;35(2):79–86. https://doi.org/10.1080/08916930290016547.

    Article  CAS  PubMed  Google Scholar 

  25. Trendelenburg M, Marfurt J, Gerber I, Tyndall A, Schifferli JA. Lack of occurrence of severe lupus nephritis among anti-C1q autoantibody-negative patients. Arthritis Rheum. 1999;42(1):187–8. https://doi.org/10.1002/1529-0131(199901)42:1<187::Aid-anr24>3.0.Co;2-u.

    Article  CAS  PubMed  Google Scholar 

  26. Chauhan SK, Singh VV, Rai R, Rai M, Rai G. Differential microRNA profile and post-transcriptional regulation exist in systemic lupus erythematosus patients with distinct autoantibody specificities. J Clin Immunol. 2014;34(4):491–503. https://doi.org/10.1007/s10875-014-0008-5.

    Article  CAS  PubMed  Google Scholar 

  27. Stagakis E, Bertsias G, Verginis P, Nakou M, Hatziapostolou M, Kritikos H, et al. Identification of novel microRNA signatures linked to human lupus disease activity and pathogenesis: miR-21 regulates aberrant T cell responses through regulation of PDCD4 expression. Ann Rheum Dis. 2011;70(8):1496–506. https://doi.org/10.1136/ard.2010.139857.

    Article  CAS  PubMed  Google Scholar 

  28. Amr KS, Bayoumi FS, Elgengehy FT, Abdallah SO, Ahmed HH, Eissa E. The role of microRNA-31 and microRNA-21 as regulatory biomarkers in the activation of T lymphocytes of Egyptian lupus patients. Rheumatol Int. 2016;36(11):1617–25. https://doi.org/10.1007/s00296-016-3550-z.

    Article  CAS  PubMed  Google Scholar 

  29. Tang Y, Luo X, Cui H, Ni X, Yuan M, Guo Y, et al. MicroRNA-146A contributes to abnormal activation of the type I interferon pathway in human lupus by targeting the key signaling proteins. Arthritis Rheum. 2009;60(4):1065–75. https://doi.org/10.1002/art.24436.

    Article  CAS  Google Scholar 

  30. Zhu Y, Xue Z, Di L. Regulation of MiR-146a and TRAF6 in the diagnose of lupus nephritis. Med Sci Monit. 2017;23:2550–7. https://doi.org/10.12659/msm.900667.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Rubin LA, Urowitz MB, Gladman DD. Mortality in systemic lupus erythematosus: the bimodal pattern revisited. Q J Med. 1985;55(216):87–98. https://doi.org/10.1093/oxfordjournals.qjmed.a067857.

    Article  CAS  PubMed  Google Scholar 

  32. • Duroux-Richard I, Cuenca J, Ponsolles C, Pineiro AB, Gonzalez F, Roubert C, et al. MicroRNA profiling of B cell subsets from systemic lupus Erythematosus patients reveals promising novel biomarkers. Int J Mol Sci. 2015;16(8):16953–65. https://doi.org/10.3390/ijms160816953This study found a miRNA signature in B cells of SLE patients with the ability to distinguish SLE patients with lupus nephritis from those without and predict renal outcomes.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Navarro-Quiroz E, Pacheco-Lugo L, Lorenzi H, Diaz-Olmos Y, Almendrales L, Rico E, et al. High-throughput sequencing reveals circulating miRNAs as potential biomarkers of kidney damage in patients with systemic lupus Erythematosus. PLoS One. 2016;11(11):e0166202. https://doi.org/10.1371/journal.pone.0166202.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Cardenas-Gonzalez M, Srivastava A, Pavkovic M, Bijol V, Rennke HG, Stillman IE, et al. Identification, confirmation, and replication of novel urinary MicroRNA biomarkers in lupus nephritis and diabetic nephropathy. Clin Chem. 2017;63(9):1515–26. https://doi.org/10.1373/clinchem.2017.274175.

    Article  CAS  Google Scholar 

  35. Sole C, Cortes-Hernandez J, Felip ML, Vidal M, Ordi-Ros J. miR-29c in urinary exosomes as predictor of early renal fibrosis in lupus nephritis. Nephrol Dial Transplant. 2015;30(9):1488–96. https://doi.org/10.1093/ndt/gfv128.

    Article  CAS  PubMed  Google Scholar 

  36. Ciccacci C, Perricone C, Politi C, Rufini S, Ceccarelli F, Cipriano E, et al. A polymorphism upstream MIR1279 gene is associated with pericarditis development in systemic lupus Erythematosus and contributes to definition of a genetic risk profile for this complication. Lupus. 2017;26(8):841–8. https://doi.org/10.1177/0961203316679528.

    Article  CAS  PubMed  Google Scholar 

  37. Ding Y, Liao W, Yi Z, Xiang W, He X. Association of miRNA-145 expression in vascular smooth muscle cells with vascular damages in patients with lupus nephritis. Int J Clin Exp Pathol. 2015;8(10):12646–56.

    CAS  PubMed  PubMed Central  Google Scholar 

  38. • Kay SD, Carlsen AL, Voss A, Burton M, Diederichsen A, Poulsen MK, et al. Associations of circulating cell-free microRNA with vasculopathy and vascular events in systemic lupus erythematosus patients. Scand J Rheumatol. 2019;48(1):32–41. https://doi.org/10.1080/03009742.2018.1450892This cross-sectional study found a circulating miRNA combination that can distinguish SLE patients with atherosclerosis from those without.

    Article  CAS  PubMed  Google Scholar 

  39. Mehta A, Baltimore D. MicroRNAs as regulatory elements in immune system logic. Nat Rev Immunol. 2016;16(5):279–94. https://doi.org/10.1038/nri.2016.40.

    Article  CAS  PubMed  Google Scholar 

  40. Banchereau J, Pascual V. Type I interferon in systemic lupus erythematosus and other autoimmune diseases. Immunity. 2006;25(3):383–92. https://doi.org/10.1016/j.immuni.2006.08.010.

    Article  CAS  PubMed  Google Scholar 

  41. Baccala R, Hoebe K, Kono DH, Beutler B, Theofilopoulos AN. TLR-dependent and TLR-independent pathways of type I interferon induction in systemic autoimmunity. Nat Med. 2007;13(5):543–51. https://doi.org/10.1038/nm1590.

    Article  CAS  PubMed  Google Scholar 

  42. Shrivastav M, Niewold TB. Nucleic acid sensors and type I interferon production in systemic lupus Erythematosus. Front Immunol. 2013;4:319. https://doi.org/10.3389/fimmu.2013.00319.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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. https://doi.org/10.1073/pnas.0605298103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Luo X, Yang W, Ye DQ, Cui H, Zhang Y, Hirankarn N, et al. A functional variant in microRNA-146a promoter modulates its expression and confers disease risk for systemic lupus erythematosus. PLoS Genet. 2011;7(6):e1002128. https://doi.org/10.1371/journal.pgen.1002128.

    Article  CAS  Google Scholar 

  45. Qu B, Cao J, Zhang F, Cui H, Teng J, Li J, et al. Type I interferon inhibition of MicroRNA-146a maturation through up-regulation of monocyte chemotactic protein-induced protein 1 in systemic lupus Erythematosus. Arthritis Rheum. 2015;67(12):3209–18. https://doi.org/10.1002/art.39398.

    Article  CAS  Google Scholar 

  46. Hou J, Wang P, Lin L, Liu X, Ma F, An H, et al. MicroRNA-146a feedback inhibits RIG-I-dependent type I IFN production in macrophages by targeting TRAF6, IRAK1, and IRAK2. J Immunol. 2009;183(3):2150–8. https://doi.org/10.4049/jimmunol.0900707.

    Article  CAS  PubMed  Google Scholar 

  47. Chan VS, Nie YJ, Shen N, Yan S, Mok MY, Lau CS. Distinct roles of myeloid and plasmacytoid dendritic cells in systemic lupus erythematosus. Autoimmun Rev. 2012;11(12):890–7. https://doi.org/10.1016/j.autrev.2012.03.004.

    Article  CAS  PubMed  Google Scholar 

  48. Karrich JJ, Jachimowski LC, Libouban M, Iyer A, Brandwijk K, Taanman-Kueter EW, et al. MicroRNA-146a regulates survival and maturation of human plasmacytoid dendritic cells. Blood. 2013;122(17):3001–9. https://doi.org/10.1182/blood-2012-12-475087.

    Article  CAS  Google Scholar 

  49. Pratama A, Srivastava M, Williams NJ, Papa I, Lee SK, Dinh XT, et al. MicroRNA-146a regulates ICOS-ICOSL signalling to limit accumulation of T follicular helper cells and germinal centres. Nat Commun. 2015;6:6436. https://doi.org/10.1038/ncomms7436.

  50. Tang Q, Yang Y, Zhao M, Liang G, Wu H, Liu Q, et al. Mycophenolic acid upregulates miR-142-3P/5P and miR-146a in lupus CD4+T cells. Lupus. 2015;24(9):935–42. https://doi.org/10.1177/0961203315570685.

    Article  CAS  Google Scholar 

  51. Pan Y, Jia T, Zhang Y, Zhang K, Zhang R, Li J, et al. MS2 VLP-based delivery of microRNA-146a inhibits autoantibody production in lupus-prone mice. Int J Nanomedicine. 2012;7:5957–67. https://doi.org/10.2147/ijn.S37990.

  52. Liang D, Zhou S, Liu Z, Shan Z, Brohawn P, Yao Y, et al. In Vivo Administration Of MiR-146a Protects C57BL/6 Mice From Pristane-Induced Pulmonary Hemorrhage Via Suppressing Type I Interferon Response. Arthritis Rheum. 2013;65:S1162.

    Google Scholar 

  53. Wang P, Hou J, Lin L, Wang C, Liu X, Li D, et al. Inducible microRNA-155 feedback promotes type I IFN signaling in antiviral innate immunity by targeting suppressor of cytokine signaling 1. J Immunol. 2010;185(10):6226–33. https://doi.org/10.4049/jimmunol.1000491.

    Article  CAS  PubMed  Google Scholar 

  54. Davis TE, Kis-Toth K, Tsokos GC. Methylprednisolone-Induced Inhibition of miR-155 Expression Increases SOCS1-Driven Suppression of Cytokine Signaling. Arthritis Rheum. 2014;66:S151-S. https://doi.org/10.1002/art.38535.

    Article  Google Scholar 

  55. Divekar AA, Dubey S, Gangalum PR, Singh RR. Dicer insufficiency and MicroRNA-155 overexpression in lupus regulatory T cells: An apparent paradox in the setting of an inflammatory milieu. J Immunol. 2011;186(2):924–30. https://doi.org/10.4049/jimmunol.1002218.

    Article  CAS  PubMed  Google Scholar 

  56. Thai TH, Patterson HC, Pham DH, Kis-Toth K, Kaminski DA, Tsokos GC. Deletion of microRNA-155 reduces autoantibody responses and alleviates lupus-like disease in the Fas (lpr) mouse. Proc Natl Acad Sci U S A. 2013;110(50):20194–9. https://doi.org/10.1073/pnas.1317632110.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Aboelenein HR, Hamza MT, Marzouk H, Youness RA, Rahmoon M, Salah S, et al. Reduction of CD19 autoimmunity marker on B cells of paediatric SLE patients through repressing PU.1/TNF-alpha/BAFF axis pathway by miR-155. Growth Factors. 2017;35(2–3):49–60. https://doi.org/10.1080/08977194.2017.1345900.

    Article  CAS  Google Scholar 

  58. Leiss H, Salzberger W, Jacobs B, Gessl I, Kozakowski N, Bluml S, et al. MicroRNA 155-deficiency leads to decreased autoantibody levels and reduced severity of nephritis and pneumonitis in pristane-induced lupus. PLoS One. 2017;12(7):e0181015. https://doi.org/10.1371/journal.pone.0181015.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Xin Q, Li J, Dang J, Bian X, Shan S, Yuan J, et al. miR-155 Deficiency Ameliorates Autoimmune Inflammation of Systemic Lupus Erythematosus by Targeting S1pr1 in Faslpr/lpr Mice. J Immunol. 2015;194(11):5437–45. https://doi.org/10.4049/jimmunol.1403028.

    Article  CAS  PubMed  Google Scholar 

  60. • Zhou S, Wang Y, Meng Y, Xiao C, Liu Z, Brohawn P, et al. In Vivo Therapeutic Success of MicroRNA-155 Antagomir in a Mouse Model of Lupus Alveolar Hemorrhage. Arthritis Rheum. 2016;68(4):953–64. https://doi.org/10.1002/art.39485This study found that miR-155 antagomir ameliorated lupus lung hemorrhage.

    Article  CAS  Google Scholar 

  61. Richardson B, Scheinbart L, Strahler J, Gross L, Hanash S, Johnson M. Evidence for impaired T cell DNA methylation in systemic lupus erythematosus and rheumatoid arthritis. Arthritis Rheum. 1990;33(11):1665–73. https://doi.org/10.1002/art.1780331109.

    Article  CAS  PubMed  Google Scholar 

  62. Zhao M, Liu S, Luo S, Wu H, Tang M, Cheng W, et al. DNA methylation and mRNA and microRNA expression of SLE CD4+ T cells correlate with disease phenotype. J Autoimmun. 2014;54:127–36. https://doi.org/10.1016/j.jaut.2014.07.002.

    Article  CAS  Google Scholar 

  63. Pan W, Zhu S, Yuan M, Cui H, Wang L, Luo X, et al. MicroRNA-21 and microRNA-148a contribute to DNA hypomethylation in lupus CD4+ T cells by directly and indirectly targeting DNA methyltransferase 1. J Immunol. 2010;184(12):6773–81. https://doi.org/10.4049/jimmunol.0904060.

    Article  CAS  PubMed  Google Scholar 

  64. Zhao M, Li MY, Gao XF, Jia SJ, Gao KQ, Zhou Y, et al. Downregulation of BDH2 modulates iron homeostasis and promotes DNA demethylation in CD4(+) T cells of systemic lupus erythematosus. Clin Immunol. 2018;187:113–21. https://doi.org/10.1016/j.clim.2017.11.002.

    Article  CAS  PubMed  Google Scholar 

  65. Garchow BG, Bartulos Encinas O, Leung YT, Tsao PY, Eisenberg RA, Caricchio R, et al. Silencing of microRNA-21 in vivo ameliorates autoimmune splenomegaly in lupus mice. EMBO Mol Med. 2011;3(10):605–15. https://doi.org/10.1002/emmm.201100171.

    Article  CAS  Google Scholar 

  66. Zhao X, Tang Y, Qu B, Cui H, Wang S, Wang L, et al. MicroRNA-125a contributes to elevated inflammatory chemokine RANTES levels via targeting KLF13 in systemic lupus erythematosus. Arthritis Rheum. 2010;62(11):3425–35. https://doi.org/10.1002/art.27632.

    Article  CAS  PubMed  Google Scholar 

  67. Pan W, Zhu S, Dai D, Liu Z, Li D, Li B, et al. MiR-125a targets effector programs to stabilize Treg-mediated immune homeostasis. Nat Commun. 2015;6:7096. https://doi.org/10.1038/ncomms8096.

  68. Kotake S, Udagawa N, Takahashi N, Matsuzaki K, Itoh K, Ishiyama S, et al. IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis. J Clin Invest. 1999;103(9):1345–52. https://doi.org/10.1172/jci5703.

    Article  CAS  Google Scholar 

  69. Komiyama Y, Nakae S, Matsuki T, Nambu A, Ishigame H, Kakuta S, et al. IL-17 plays an important role in the development of experimental autoimmune encephalomyelitis. J Immunol. 2006;177(1):566–73. https://doi.org/10.4049/jimmunol.177.1.566.

    Article  CAS  PubMed  Google Scholar 

  70. Wong CK, Ho CY, Li EK, Lam CW. Elevation of proinflammatory cytokine (IL-18, IL-17, IL-12) and Th2 cytokine (IL-4) concentrations in patients with systemic lupus erythematosus. Lupus. 2000;9(8):589–93. https://doi.org/10.1191/096120300678828703.

    Article  CAS  PubMed  Google Scholar 

  71. Zhu S, Pan W, Song X, Liu Y, Shao X, Tang Y, et al. The microRNA miR-23b suppresses IL-17-associated autoimmune inflammation by targeting TAB2, TAB3 and IKK-alpha. Nat Med. 2012;18(7):1077–86. https://doi.org/10.1038/nm.2815This study found that miR-23b mimics inhibited IL-17 singaling pathway and ameliorated lupus nephritis.

    Article  CAS  PubMed  Google Scholar 

  72. Zhou H, Hasni SA, Perez P, Tandon M, Jang SI, Zheng C, et al. miR-150 promotes renal fibrosis in lupus nephritis by downregulating SOCS1. J Am Soc Nephrol. 2013;24(7):1073–87. https://doi.org/10.1681/asn.2012080849.

    Article  CAS  Google Scholar 

  73. Gao S, Yuan L, Wang Y, Hua C. Enhanced expression of TREM-1 in splenic cDCs in lupus prone mice and it was modulated by miRNA-150. Mol Immunol. 2017;81:127–34. https://doi.org/10.1016/j.molimm.2016.12.006.

    Article  CAS  PubMed  Google Scholar 

  74. • Luan J, Fu J, Chen C, Jiao C, Kong W, Zhang Y, et al. LNA-anti-miR-150 ameliorated kidney injury of lupus nephritis by inhibiting renal fibrosis and macrophage infiltration. Arthritis Res Ther. 2019;21(1):276. https://doi.org/10.1186/s13075-019-2044-2This study found that inhibition of miR-150 could ameliorate renal injury.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Liu L, Liu Y, Yuan M, Xu L, Sun H. Elevated expression of microRNA-873 facilitates Th17 differentiation by targeting forkhead box O1 (Foxo1) in the pathogenesis of systemic lupus erythematosus. Biochem Biophys Res Commun. 2017;492(3):453–60. https://doi.org/10.1016/j.bbrc.2017.08.075.

    Article  CAS  PubMed  Google Scholar 

  76. Cheng J, Wu R, Long L, Su J, Liu J, Wu XD, et al. miRNA-451a targets IFN regulatory factor 8 for the progression of systemic lupus Erythematosus. Inflammation. 2017;40(2):676–87. https://doi.org/10.1007/s10753-017-0514-8.

    Article  CAS  Google Scholar 

  77. . Li X, Luo F, Li J, Luo C. MiR-183 delivery attenuates murine lupus nephritis-related injuries via targeting mTOR. Scand J Immunol. 2019;90(5):e12810. https://doi.org/10.1111/sji.12810This study found that miR-183 could ameliorate SLE manifestations.

    Article  CAS  PubMed  Google Scholar 

  78. Qingjuan L, Xiaojuan F, Wei Z, Chao W, Pengpeng K, Hongbo L, et al. miR-148a-3p overexpression contributes to glomerular cell proliferation by targeting PTEN in lupus nephritis. Am J Phys Cell Physiol. 2016;310(6):C470–8. https://doi.org/10.1152/ajpcell.00129.2015.

    Article  Google Scholar 

  79. Han X, Wang Y, Zhang X, Qin Y, Qu B, Wu L, et al. MicroRNA-130b Ameliorates Murine Lupus Nephritis Through Targeting the Type I Interferon Pathway on Renal Mesangial Cells. Arthritis Rheum. 2016;68(9):2232–43. https://doi.org/10.1002/art.39725This study found that miR-130b mimics inhibited IFN-driven lupus nephritis.

    Article  CAS  Google Scholar 

  80. Wang X, Wang G, Zhang X, Dou Y, Dong Y, Liu D, et al. Inhibition of microRNA-182-5p contributes to attenuation of lupus nephritis via Foxo1 signaling. Exp Cell Res. 2018;373(1–2):91–8. https://doi.org/10.1016/j.yexcr.2018.09.026.

    Article  CAS  Google Scholar 

  81. Koutsokeras T, Healy T. Systemic lupus erythematosus and lupus nephritis. Nat Rev Drug Discov. 2014;13(3):173–4. https://doi.org/10.1038/nrd4227.

    Article  CAS  PubMed  Google Scholar 

  82. Davis TE, Kis-Toth K, Szanto A, Tsokos GC. Glucocorticoids suppress T cell function by up-regulating microRNA-98. Arthritis Rheum. 2013;65(7):1882–90. https://doi.org/10.1002/art.37966.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This study was supported by National Natural Science Foundation of China (31930037, 31630021, 81701603), Shanghai Pujiang Program (2019PJD028), Shanghai Municipal Key Medical Center Construction Project (2017ZZ01024–002), Sanming Project of Medicine in Shenzhen (SZSM201602087), Shenzhen Futian Public Welfare Scientific Research Project (FTWS2018005), Medical Scientific Research Foundation of Guangdong Province (A2018089).

Author information

Author notes

  1. Soon-Min Hong, Can Liu and Zhihua Yin contributed equally to this work.

Authors and Affiliations

  1. Department of Rheumatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Shandong Middle Road, Shanghai, 200001, China

    Soon-Min Hong, Can Liu, Lingling Wu, Bo Qu & Nan Shen

  2. Shenzhen Futian Hospital for Rheumatic Diseases, Shenzhen, 518040, China

    Zhihua Yin, Bo Qu & Nan Shen

  3. Center for Autoimmune Genomics and Etiology (CAGE), Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Nan Shen

  4. Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA

    Nan Shen

  5. State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, 200032, China

    Nan Shen

Authors
  1. Soon-Min Hong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Can Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zhihua Yin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lingling Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Bo Qu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Nan Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Bo Qu or Nan Shen.

Ethics declarations

Conflict of Interest

All the authors have no conflicts of interest to disclose.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Systemic Lupus Erythematosus

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hong, SM., Liu, C., Yin, Z. et al. MicroRNAs in Systemic Lupus Erythematosus: a Perspective on the Path from Biological Discoveries to Clinical Practice. Curr Rheumatol Rep 22, 17 (2020). https://doi.org/10.1007/s11926-020-00895-7

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11926-020-00895-7

Keywords

Search

Navigation