Skip to main content

Advertisement

SpringerLink
Log in

MicroRNA as a potential biomarker for systemic lupus erythematosus: pathogenesis and targeted therapy

  • Review
  • Published:
Clinical and Experimental Medicine Aims and scope Submit manuscript

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease associated with hyperactive innate and adaptive immune systems that cause dermatological, cardiovascular, renal, and neuropsychiatric problems in patients. SLE's multifactorial nature and complex pathogenesis present significant challenges in its clinical classification. In addition, unpredictable treatment responses in patients emphasize the need for highly specific and sensitive SLE biomarkers that can assist in understanding the exact pathogenesis and, thereby, lead to the identification of novel therapeutic targets. Recent studies on microRNA (miRNA), a non-coding region involved in the regulation of gene expression, indicate its importance in the development of the immune system and thus in the pathogenesis of various autoimmune disorders such as SLE. miRNAs are fascinating biomarker prospects for SLE categorization and disease monitoring owing to their small size and high stability. In this paper, we have discussed the involvement of a wide range of miRNAs in the regulation of SLE inflammation and how their modulation can be a potential therapeutic approach.

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

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Data availability

Not applicable.

Abbreviations

AGO:

Argonaute

BAFF:

B-cell-activating-factor

BBB:

Blood-brain barrier

BLIMP:

B-lymphocyte-induced-maturation-protein-1

CD4+ :

Cluster-of-differentiation-4

CD40L:

CD40 ligand

CRKL:

Crk-like

CXCL2:

Chemokine-C-X-C-motif-ligand-2

DGCR8:

DiGeorge-Syndrome-critical-region-8

DNMTs:

DNA methyltransferases

DUSP:

Dual-specificity-protein-phosphatase

EGR1:

Early-growth-response-protein-1

Foxo1:

Forkhead-box-protein-O-1

Gadd45a:

Growth-arrest-and-DNA-damage-inducible-protein-45-alpha

IFIT1:

Interferon-induced-protein-with-tetratricopeptide-repeats-1

IFN:

Interferon

Ig:

Immunoglobulin

IL:

Interleukin

IRAK1:

IL-1-receptor-associated-kinase-1

IRAKM:

Interleukin-1-receptor-associated-kinase-M

IRF5:

Interferon-regulatory-factor-5

JAK-STAT:

Janus-kinase-signal-transducers-and-activators-of-transcription

KLF13:

Kruppel-like-factor 13

miRNA:

MicroRNA

MyD88:

Myeloid-differentiation-protein-88

NETs:

Neutrophil Extracellular Traps

NFκB:

Nuclear-factor-kappa-B

PBMCs:

Peripheral blood mononuclear cells

PDCD4:

Programmed-cell-death 4

pDCs:

Plasmacytoid dendritic cells

pre-miRNA:

Precursor-miRNA

pri-miRNA:

Primary miRNA

PRRs:

Pattern recognition receptors

PTEN:

Phosphatase-and-tensin-homolog

PTPN22:

Protein-tyrosine-phosphatase-non-receptor-type 22

Ran:

RAs-related-nuclear-protein

RASGRP1:

RAS-guanyl- nucleotide-releasing-protein

RIG:

Retinoic-acid inducible gene

RISC:

RNA-induced-silencing-complex

SHP-2:

Src-homology-region-2

SLE:

Systemic lupus erythematosus

SNP:

Single-nucleotide polymorphism

SOCS:

Suppressors-of-cytokine-signaling

SPI1 or PU.1:

Spi-1-proto-oncogene

STAM:

Signal-transducing-adapter-molecule

STAT1:

Signal-transducer-and-activator-of-transcription-1

TAB2:

TGF-beta-activated-kinase-1-(MAP3K7)-binding-protein-2

TCR:

T-cell receptors

Th:

T-helper

TLRs:

Toll-like receptors

TRAF6:

TNF-receptor-associated-factor-6

T-reg:

T regulatory

UTRs:

Untranslated regions

XPO5:

Exportin 5

References

  1. Barber MRW, Drenkard C, Falasinnu T, et al. Global epidemiology of systemic lupus erythematosus. Nat Rev Rheumatol. 2021;17:515–32. https://doi.org/10.1038/s41584-021-00668-1.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Kane BS, Niasse M, Ndiaye AA, et al. Systemic diseases in Dakar (Senegal): spectrum, epidemiological aspect and diagnostic time-limit. Open J Intern Med. 2018;08:196–206. https://doi.org/10.4236/ojim.2018.83019.

    Article  Google Scholar 

  3. Grennan DM, Bossingham D. Systemic lupus erythematosus (SLE): different prevalences in different populations of Australian aboriginals. Aust N Z J Med. 1995;25:182–3. https://doi.org/10.1111/j.1445-5994.1995.tb02843.x.

    Article  CAS  PubMed  Google Scholar 

  4. Magro R, Borg AA. Characterisation of patients with systemic lupus erythematosus in Malta: a population based cohort cross-sectional study. BioMed Res Int. 2018;2018:2385386. https://doi.org/10.1155/2018/2385386.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Anstey NM, Bastian I, Dunckley H, Currie BJ. Systemic lupus erythematosus in Australian aborigines: high prevalence, morbidity and mortality. Aust N Z J Med. 1993;23:646–51. https://doi.org/10.1111/j.1445-5994.1993.tb04720.x.

    Article  CAS  PubMed  Google Scholar 

  6. Tan G, Baby B, Zhou Y, Wu T. Emerging molecular markers towards potential diagnostic panels for lupus. Front Immunol. 2021;12:808839. https://doi.org/10.3389/fimmu.2021.808839.

    Article  CAS  PubMed  Google Scholar 

  7. Nossent J, Kiss E, Rozman B, et al. Disease activity and damage accrual during the early disease course in a multinational inception cohort of patients with systemic lupus erythematosus. Lupus. 2010;19:949–56. https://doi.org/10.1177/0961203310366572.

    Article  CAS  PubMed  Google Scholar 

  8. Katsuyama T, Tsokos GC, Moulton VR. Aberrant T cell signaling and subsets in systemic lupus erythematosus. Front Immunol. 2018;9:1088. https://doi.org/10.3389/fimmu.2018.01088.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Karrar S, Cunninghame Graham DS. Abnormal B cell development in systemic lupus erythematosus. Arthritis Rheumatol. 2018;70:496–507. https://doi.org/10.1002/art.40396.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Yu H, Nagafuchi Y, Fujio K. Clinical and immunological biomarkers for systemic lupus erythematosus. Biomolecules. 2021;11:928. https://doi.org/10.3390/biom11070928.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Wang W, Yue C, Gao S, et al. Promising roles of exosomal microRNAs in systemic lupus erythematosus. Front Immunol. 2021;12:757096. https://doi.org/10.3389/fimmu.2021.757096.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Hong SM, Liu C, Yin Z, Wu L, Qu B, Shen N. MicroRNAs in systemic lupus erythematosus: a perspective on the path from biological discoveries to clinical practice. Curr Rheumatol Rep. 2020;22:17. https://doi.org/10.1007/s11926-020-00895-7.

    Article  CAS  PubMed  Google Scholar 

  13. Zhang L, Wu H, Zhao M, Chang C, Lu Q. Clinical significance of miRNAs in autoimmunity. J Autoimmun. 2020;109:102438. https://doi.org/10.1016/j.jaut.2020.102438.

    Article  CAS  PubMed  Google Scholar 

  14. Kai K, Dittmar RL, Sen S. Secretory microRNAs as biomarkers of cancer. Semin Cell Dev Biol. 2018;78:22–36. https://doi.org/10.1016/j.semcdb.2017.12.011.

    Article  CAS  PubMed  Google Scholar 

  15. O’Brien J, Hayder H, Zayed Y, Peng C. Overview of MicroRNA biogenesis, mechanisms of actions, and circulation. Front Endocrinol. 2018;9:402. https://doi.org/10.3389/fendo.2018.00402.

    Article  Google Scholar 

  16. Pal AS, Kasinski AL. Animal models to study microRNA function. Adv Cancer Res. 2017;135:53–118. https://doi.org/10.1016/bs.acr.2017.06.006.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Condrat CE, Thompson DC, Barbu MG, et al. miRNAs as biomarkers in disease: latest findings regarding their role in diagnosis and prognosis. Cells. 2020;9:276.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Lopez-Pedrera C, Barbarroja N, Patiño-Trives AM, et al. Role of microRNAs in the development of cardiovascular disease in systemic autoimmune disorders. Int J Mol Sci. 2020;21:2012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Hussein M, Magdy R. MicroRNAs in central nervous system disorders: current advances in pathogenesis and treatment. Egypt J Neurol Psychiatry Neurosurg. 2021;57:36. https://doi.org/10.1186/s41983-021-00289-1.

    Article  Google Scholar 

  20. Lan H, Lu H, Wang X, Jin H. MicroRNAs as potential biomarkers in cancer: opportunities and challenges. BioMed Res Int. 2015;2015:125094. https://doi.org/10.1155/2015/125094.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Honarpisheh M, Köhler P, von Rauchhaupt E, Lech M. The involvement of MicroRNAs in modulation of innate and adaptive immunity in systemic lupus erythematosus and lupus nephritis. J Immunol Res. 2018;2018:4126106. https://doi.org/10.1155/2018/4126106.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Treiber T, Treiber N, Meister G. Regulation of microRNA biogenesis and its crosstalk with other cellular pathways. Nat Rev Mol Cell Biol. 2019;20:5–20. https://doi.org/10.1038/s41580-018-0059-1.

    Article  CAS  PubMed  Google Scholar 

  23. Schell SL, Rahman ZSM. miRNA-mediated control of B cell responses in immunity and SLE. Front Immunol. 2021;12: 683710. https://doi.org/10.3389/fimmu.2021.683710.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Chi SW, Zang JB, Mele A, Darnell RB. Argonaute HITS-CLIP decodes microRNA-mRNA interaction maps. Nature. 2009;460:479–86. https://doi.org/10.1038/nature08170.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cel. 2005;120:15–20. https://doi.org/10.1016/j.cell.2004.12.035.

    Article  CAS  Google Scholar 

  26. Lee I, Ajay SS, Yook JI, et al. New class of microRNA targets containing simultaneous 5′-UTR and 3′-UTR interaction sites. Genome Res. 2009;19:1175–83. https://doi.org/10.1101/gr.089367.108.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Denzler R, McGeary SE, Title AC, Agarwal V, Bartel DP, Stoffel M. Impact of MicroRNA levels, target-site complementarity, and cooperativity on competing endogenous RNA-regulated gene expression. Mol Cell. 2016;64:565–79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Landgraf P, Rusu M, Sheridan R, et al. A mammalian microRNA expression atlas based on small RNA library sequencing. Cell. 2007;129:1401–14. https://doi.org/10.1016/j.cell.2007.04.040.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Hsin JP, Lu Y, Loeb GB, Leslie CS, Rudensky AY. The effect of cellular context on miR-155-mediated gene regulation in four major immune cell types. Nat Immunol. 2018;19:1137–45. https://doi.org/10.1038/s41590-018-0208-x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Carlsen AL, Schetter AJ, Nielsen CT, et al. Circulating microRNA expression profiles associated with systemic lupus erythematosus. Arthritis Rheum. 2013;65:1324–34. https://doi.org/10.1002/art.37890.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Luo X, Tsai LM, Shen N, Yu D. Evidence for microRNA-mediated regulation in rheumatic diseases. Ann Rheum Dis. 2010;1:30–6. https://doi.org/10.1136/ard.2009.117218.

    Article  CAS  Google Scholar 

  32. Dai Y, Sui W, Lan H, Yan Q, Huang H, Huang Y. Comprehensive analysis of microRNA expression patterns in renal biopsies of lupus nephritis patients. Rheumatol Int. 2009;29:749–54. https://doi.org/10.1007/s00296-008-0758-6.

    Article  CAS  PubMed  Google Scholar 

  33. Te JL, Dozmorov IM, Guthridge JM, et al. Identification of unique microRNA signature associated with lupus nephritis. PLoS ONE. 2010;5:10344. https://doi.org/10.1371/journal.pone.0010344.

    Article  CAS  Google Scholar 

  34. Zhang X, Yao B, Hu Q, et al. Detection of biomarkers in body fluids using bioprobes based on aggregation-induced emission fluorogens. Mater Chem Front. 2010;4:2548–70. https://doi.org/10.1039/D0QM00376J.

    Article  Google Scholar 

  35. Aristizábal B, González Á, et al. Innate immune system. In: Anaya JM, Shoenfeld Y, Rojas-Villarraga A, et al., editors. Autoimmunity: From Bench to Bedside. Bogota: El Rosario University Press; 2013.

    Google Scholar 

  36. Lamkanfi M, Dixit VM. Inflammasomes and their roles in health and disease. Annu Rev Cell Dev Biol. 2012;28:137–61. https://doi.org/10.1146/annurev-cellbio-101011-155745.

    Article  CAS  PubMed  Google Scholar 

  37. Medzhitov R, Janeway CA. Innate immunity: impact on the adaptive immune response. Curr Opin Immunol. 1997;9:4–9. https://doi.org/10.1016/s0952-7915(97)80152-5.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  39. Shrivastav M, Niewold TB. Nucleic acid sensors and type I interferon production in systemic lupus erythematosus. Front Immunol. 2013;4:319.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Tang Y, Luo X, Cui H, 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;60:1065–75. https://doi.org/10.1002/art.24436.

    Article  CAS  PubMed  Google Scholar 

  41. Luo X, Yang W, Ye DQ, et al. A functional variant in MicroRNA-146a promoter modulates its expression and confers disease risk for systemic lupus erythematosus. PLoS Genet. 2011;7:1002128.

    Article  Google Scholar 

  42. Hou J, Wang P, Lin L, et al. MicroRNA-146a feedback inhibits RIG-I-dependent Type I IFN production in macrophages by targeting TRAF6, IRAK1, and IRAK2. J Immunol. 2009;83:2150–8. https://doi.org/10.4049/jimmunol.0900707.

    Article  CAS  Google Scholar 

  43. Hsieh YT, Chou YC, Kuo PY, et al. Down-regulated miR-146a expression with increased neutrophil extracellular traps and apoptosis formation in autoimmune-mediated diffuse alveolar hemorrhage. J Biomed Sci. 2022;29:62. https://doi.org/10.1186/s12929-022-00849-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. 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;103:12481–6. https://doi.org/10.1073/pnas.0605298103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Tang B, Xiao B, Liu Z, et al. Identification of MyD88 as a novel target of miR-155, involved in negative regulation of Helicobacter pylori-induced inflammation. FEBS Lett. 2010;584:1481–6. https://doi.org/10.1016/j.febslet.2010.02.063.

    Article  CAS  PubMed  Google Scholar 

  46. von Bernuth H, Picard C, Jin Z, et al. Pyogenic bacterial infections in humans with MyD88 deficiency. Science. 2008;321:691–6. https://doi.org/10.1126/science.1158298.

    Article  CAS  Google Scholar 

  47. Zhou H, Huang X, Cui H, et al. miR-155 and its star-form partner miR-155* cooperatively regulate type I interferon production by human plasmacytoid dendritic cells. Blood. 2010;116:5885–94. https://doi.org/10.1182/blood-2010-04-280156.

    Article  CAS  PubMed  Google Scholar 

  48. Gilliet M, Cao W, Liu YJ. Plasmacytoid dendritic cells: sensing nucleic acids in viral infection and autoimmune diseases. Nat Rev Immunol. 2008;8:594–606. https://doi.org/10.1038/nri2358.

    Article  CAS  PubMed  Google Scholar 

  49. Aboelenein HR, Hamza MT, Marzouk H, et al. Reduction of CD19 autoimmunity marker on B cells of paediatric SLE patients through repressing PU.1/TNF-α/BAFF axis pathway by miR-155. Growth Fact. 2017;35:49–60. https://doi.org/10.1080/08977194.2017.1345900.

    Article  CAS  Google Scholar 

  50. Mishra R, Bhattacharya S, Rawat BS, et al. MicroRNA-30e-5p has an integrated role in the regulation of the innate immune response during virus infection and systemic lupus erythematosus. iScience. 2020;23:101322.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Yang B, Huang X, Xu S, et al. Decreased miR-4512 levels in monocytes and macrophages of individuals with systemic lupus erythematosus contribute to innate immune activation and neutrophil NETosis by targeting TLR4 and CXCL2. Front Immunol. 2021;12:756825. https://doi.org/10.3389/fimmu.2021.756825.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Wang Y, Liu X, Xia P, et al. The regulatory role of MicroRNAs on phagocytes: a potential therapeutic target for chronic diseases. Front Immunol. 2022;13:901166. https://doi.org/10.3389/fimmu.2022.901166.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Yan L, Jiang L, Wang B, et al. Novel microRNA biomarkers of systemic lupus erythematosus in plasma: miR-124-3p and miR-377-3p. Clin Biochem. 2022;107:55–61. https://doi.org/10.1016/j.clinbiochem.2022.05.004.

    Article  CAS  PubMed  Google Scholar 

  54. Ahmed MM, Zaki A, Alhazmi A, et al. Identification and validation of pathogenic genes in sepsis and associated diseases by integrated bioinformatics approach. Genes. 2022;13:209. https://doi.org/10.3390/genes13020209.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Gupta S, Kaplan MJ. The role of neutrophils and NETosis in autoimmune and renal diseases. Nat Rev Nephrol. 2006;12:402–13. https://doi.org/10.1038/nrneph.2016.71.

    Article  CAS  Google Scholar 

  56. Sadeghi M, Dehnavi S, Jamialahmadi T, Johnston TP, Sahebkar A. Neutrophil extracellular trap: a key player in the pathogenesis of autoimmune diseases. Int Immunopharmacol. 2023;116:109843. https://doi.org/10.1016/j.intimp.2023.109843.

    Article  CAS  PubMed  Google Scholar 

  57. Blanco LP, Wang X, Carlucci PM, et al. RNA externalized by neutrophil extracellular traps promotes inflammatory pathways in endothelial cells. Arthritis Rheumatol. 2021;73:2282–92. https://doi.org/10.1002/art.41796.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Deng Y, Zhao J, Sakurai D, et al. MicroRNA-3148 modulates allelic expression of toll-like receptor 7 variant associated with systemic lupus erythematosus. PLoS Genet. 2013;9:1003336. https://doi.org/10.1371/journal.pgen.1003336.

    Article  CAS  Google Scholar 

  59. Chafin CB, Regna NL, Dai R, Caudell DL, Reilly CM. MicroRNA-let-7a expression is increased in the mesangial cells of NZB/W mice and increases IL-6 production in vitro. Autoimmunity. 2013;46:351–62. https://doi.org/10.3109/08916934.2013.773976.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Kim SJ, Gregersen PK, Diamond B. Regulation of dendritic cell activation by microRNA let-7c and BLIMP1. J Clin Invest. 2013;1232:823–33.

    Google Scholar 

  61. Smith S, Wu PW, Seo JJ, et al. IL-16/miR-125a axis controls neutrophil recruitment in pristane-induced lung inflammation. JCI Insight. 2018;3:120798. https://doi.org/10.1172/jci.insight.120798.

    Article  PubMed  Google Scholar 

  62. Bonilla FA, Oettgen HC. Adaptive immunity. J Allergy Clin Immunol. 2010;125:33–40. https://doi.org/10.1016/j.jaci.2009.09.017.

    Article  Google Scholar 

  63. Hirschberger S, Hinske LC, Kreth S. MiRNAs: dynamic regulators of immune cell functions in inflammation and cancer. Cancer Lett. 2018;431:11–21. https://doi.org/10.1016/j.canlet.2018.05.020.

    Article  CAS  PubMed  Google Scholar 

  64. Kourti M, Sokratous M, Katsiari CG. Regulation of microRNA in systemic lupus erythematosus: the role of miR-21 and miR-210. Mediterr J Rheumatol. 2020;31:71–4.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Chi M, Ma K, Li Y, et al. Immunological involvement of MicroRNAs in the key events of systemic lupus erythematosus. Front Immunol. 2021;12:699684. https://doi.org/10.3389/fimmu.2021.699684.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Zan H, Tat C, Casali P. MicroRNAs in lupus. Autoimmunity. 2014;47:272–85. https://doi.org/10.3109/08916934.2014.915955.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Cobb BS, Hertweck A, Smith J, et al. A role for Dicer in immune regulation. J Exp Med. 2006;203:2519–27. https://doi.org/10.1084/jem.20061692.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Chen SH, Lv QL, Hu L, Peng MJ, Wang GH, Sun B. DNA methylation alterations in the pathogenesis of lupus. Clin Exp Immunol. 2017;187:185–92.

    Article  CAS  PubMed  Google Scholar 

  69. Pan W, Zhu S, Yuan M, 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;1950(184):6773–81. https://doi.org/10.4049/jimmunol.0904060.

    Article  CAS  Google Scholar 

  70. Qin H, Zhu X, Liang J, et al. MicroRNA-29b contributes to DNA hypomethylation of CD4+ T cells in systemic lupus erythematosus by indirectly targeting DNA methyltransferase 1. J Dermatol Sci. 2013;69:61–7. https://doi.org/10.1016/j.jdermsci.2012.10.011.

    Article  CAS  PubMed  Google Scholar 

  71. Zhao S, Wang Y, Liang Y, et al. MicroRNA-126 regulates DNA methylation in CD4+ T cells and contributes to systemic lupus erythematosus by targeting DNA methyltransferase 1. Arthritis Rheum. 2011;63:1376–86. https://doi.org/10.1002/art.30196.

    Article  CAS  PubMed  Google Scholar 

  72. Stagakis E, Bertsias G, Verginis P, 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;70:1496–506. https://doi.org/10.1136/ard.2010.139857.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  74. Al-hasso IK, Al-Derzi AR, Abbas AA, Gorial FI, Alnuimi AS. The role of microRNAs (MiR-125a and MiR-146a), RANTES, and IFN-γin systemic lupus erythematosus. Ann Trop Med Public Health. 2020. https://doi.org/10.36295/asro.2020.231382.

    Article  Google Scholar 

  75. Motawi TK, Mohsen DA, El-Maraghy SA, Kortam MA. MicroRNA-21, microRNA-181a and microRNA-196a as potential biomarkers in adult Egyptian patients with systemic lupus erythematosus. Chem Biol Interact. 2016;260:110–6. https://doi.org/10.1016/j.cbi.2016.11.001.

    Article  CAS  PubMed  Google Scholar 

  76. Abdul-Maksoud RS, Rashad NM, Elsayed WSH, Ali MA, Kamal NM, Zidan HE. Circulating miR-181a and miR-223 expression with the potential value of biomarkers for the diagnosis of systemic lupus erythematosus and predicting lupus nephritis. J Gene Med. 2021;23:3326. https://doi.org/10.1002/jgm.3326.

    Article  CAS  Google Scholar 

  77. Li HS, Ning Y, Li SB, et al. Expression and clinical significance of miR-181a and miR-203 in systemic lupus erythematosus patients. Eur Rev Med Pharmacol Sci. 2017;21:4790–6.

    PubMed  Google Scholar 

  78. 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;186:924–30. https://doi.org/10.4049/jimmunol.1002218.

    Article  CAS  PubMed  Google Scholar 

  79. Wang H, Geng G, Zhang D, Han F, Ye S. Analysis of microRNA-199a-3p expression in CD4+ T cells of systemic lupus erythematosus. Clin Rheumatol. 2023;42:1683–94. https://doi.org/10.1007/s10067-023-06534-7.

    Article  PubMed  Google Scholar 

  80. Wang Z, Heid B, Lu R, et al. Deletion of microRNA-183-96-182 cluster in lymphocytes suppresses Anti-DsDNA autoantibody production and IgG deposition in the kidneys in C57BL/6-Faslpr/lpr Mice. Front Genet. 2022;13:840060. https://doi.org/10.3389/fgene.2022.840060.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Wang Z, Dai R, Ahmed SA. MicroRNA-183/96/182 cluster in immunity and autoimmunity. Front Immunol. 2023;14:1134634. https://doi.org/10.3389/fimmu.2023.1134634.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Brandl A, Daum P, Brenner S, et al. The microprocessor component, DGCR8, is essential for early B-cell development in mice. Eur J Immunol. 2016;46:2710–8. https://doi.org/10.1002/eji.201646348.

    Article  CAS  PubMed  Google Scholar 

  83. Gonzalez-Martin A, Adams BD, Lai M, et al. The microRNA miR-148a functions as a critical regulator of B cell tolerance and autoimmunity. Nat Immunol. 2016;17:433–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Humayun A, Fornace AJ. Gadd45 in stress signaling, cell cycle control, and apoptosis. Adv Exp Med Biol. 2022;1360:1–22. https://doi.org/10.1007/978-3-030-94804-7_1.

    Article  CAS  PubMed  Google Scholar 

  85. Ibrahim SA, Afify AY, Fawzy IO, El-Ekiaby N, Abdelaziz AI. The curious case of miR-155 in SLE. Expert Rev Mol Med. 2021;23:11. https://doi.org/10.1017/erm.2021.11.

    Article  CAS  Google Scholar 

  86. Aiello FB, Guszczynski T, Li W, et al. IL-7-induced phosphorylation of the adaptor Crk-like and other targets. Cell Signal. 2018;47:131–41. https://doi.org/10.1016/j.cellsig.2018.03.008.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Shi X, Ye L, Xu S, et al. Downregulated miR-29a promotes B cell overactivation by upregulating Crk-like protein in systemic lupus erythematosus. Mol Med Rep. 2020;22:841–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Xia Y, Tao JH, Fang X, et al. MicroRNA-326 upregulates B cell activity and autoantibody production in lupus disease of MRL/lpr mice. Mol Ther Nucleic Acids. 2018;11:284–91.

    Article  PubMed  PubMed Central  Google Scholar 

  89. Jin L, Fang X, Dai C, et al. The potential role of Ets-1 and miR-326 in CD19+B cells in the pathogenesis of patients with systemic lupus erythematosus. Clin Rheumatol. 2019;38:1031–8. https://doi.org/10.1007/s10067-018-4371-0.

    Article  PubMed  Google Scholar 

  90. Talaat RM, Mohamed SF, Bassyouni IH, Raouf AA. Th1/Th2/Th17/Treg cytokine imbalance in systemic lupus erythematosus (SLE) patients: correlation with disease activity. Cytokine. 2015;72:146–53. https://doi.org/10.1016/j.cyto.2014.12.027.

    Article  CAS  PubMed  Google Scholar 

  91. Arkatkar T, Du SW, Jacobs HM, et al. B cell–derived IL-6 initiates spontaneous germinal center formation during systemic autoimmunity. J Exp Med. 2017;214:3207–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Fava A, Petri M. Systemic lupus erythematosus: diagnosis and clinical management. J Autoimmun. 2019;96:1–13. https://doi.org/10.1016/J.JAUT.2018.11.001.

    Article  PubMed  Google Scholar 

  93. Kirou KA, Dall`Era M, Aranow C, Anders HJ. Belimumab or anifrolumab for systemic lupus erythematosus? A risk-benefit assessment. Front Immunol. 2022;13:980079. https://doi.org/10.3389/FIMMU.2022.980079/BIBTEX.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Mok CC, Tse SM, Chan KL, Ho LY. Effect of immunosuppressive therapies on survival of systemic lupus erythematosus: a propensity score analysis of a longitudinal cohort. Lupus. 2017;27(5):722–7. https://doi.org/10.1177/0961203317739129.

    Article  CAS  PubMed  Google Scholar 

  95. Cain DW, Cidlowski JA. Immune regulation by glucocorticoids. Nat Rev Immunol. 2017;17(4):233–47. https://doi.org/10.1038/nri.2017.1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Skoglund O, Walhelm T, Thyberg I, Eriksson P, Sjöwall C. Fighting fatigue in systemic lupus erythematosus: experience of dehydroepiandrosterone on clinical parameters and patient-reported outcomes. J Clin Med. 2022;11(18):5300. https://doi.org/10.3390/JCM11185300.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Fanouriakis A, Tziolos N, Bertsias G, Boumpas DT. Update οn the diagnosis and management of systemic lupus erythematosus. Ann Rheum Dis. 2021;80(1):14–25. https://doi.org/10.1136/ANNRHEUMDIS-2020-218272.

    Article  PubMed  Google Scholar 

  98. Cobo-Ibáñez T, Loza-Santamaría E, Pego-Reigosa JM, et al. Efficacy and safety of rituximab in the treatment of non-renal systemic lupus erythematosus: a systematic review. Semin Arthritis Rheum. 2014;44(2):175–85. https://doi.org/10.1016/J.SEMARTHRIT.2014.04.002.

    Article  PubMed  Google Scholar 

  99. Van Vollenhoven RF, Petri MA, Cervera R, et al. Belimumab in the treatment of systemic lupus erythematosus: high disease activity predictors of response. Ann Rheum Dis. 2012;71(8):1343–9. https://doi.org/10.1136/ANNRHEUMDIS-2011-200937.

    Article  PubMed  Google Scholar 

  100. Zhang L, Wei W. Anti-inflammatory and immunoregulatory effects of paeoniflorin and total glucosides of paeony. Pharmacol Ther. 2020;207:107452. https://doi.org/10.1016/J.PHARMTHERA.2019.107452.

    Article  CAS  PubMed  Google Scholar 

  101. Durcan L, O’Dwyer T, Petri M. Management strategies and future directions for systemic lupus erythematosus in adults. The Lancet. 2019;393(10188):2332–43. https://doi.org/10.1016/S0140-6736(19)30237-5.

    Article  Google Scholar 

  102. Parra Sánchez AR, Voskuyl AE, van Vollenhoven RF. Treat-to-target in systemic lupus erythematosus: advancing towards its implementation. Nat Rev Rheumatol. 2022;18(3):146–57. https://doi.org/10.1038/s41584-021-00739-3.

    Article  PubMed  Google Scholar 

  103. Tanaka Y. Systemic lupus erythematosus. Best Pract Res Clin Rheumatol. 2022;36(4):101814. https://doi.org/10.1016/J.BERH.2022.101814.

    Article  PubMed  Google Scholar 

  104. Chafin CB, Reilly CM. MicroRNAs implicated in the immunopathogenesis of lupus nephritis. Clin Dev Immunol. 2013;2013:430239.

    Article  PubMed  PubMed Central  Google Scholar 

  105. Thai TH, Christiansen PA, Tsokos GC. Is there a link between dysregulated miRNA expression and disease? Discov Med. 2010;10:184–94.

    PubMed  Google Scholar 

  106. Salvi V, Gianello V, Tiberio L, Sozzani S, Bosisio D. Cytokine targeting by miRNAs in autoimmune diseases. Front Immunol. 2019;10:15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Christopher AF, Kaur RP, Kaur G, Kaur A, Gupta V, Bansal P. MicroRNA therapeutics: discovering novel targets and developing specific therapy. Perspect Clin Res. 2016;7:68–74. https://doi.org/10.4103/2229-3485.179431.

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  109. 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;110:20194–9. https://doi.org/10.1073/pnas.1317632110.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Zhou S, Wang Y, Meng Y, et al. In vivo therapeutic success of MicroRNA-155 Antagomir in a mouse model of lupus alveolar hemorrhage. Arthritis Rheumatol. 2016;68:953–64. https://doi.org/10.1002/art.39485.

    Article  CAS  PubMed  Google Scholar 

  111. Wang M, Chen H, Qiu J, et al. Antagonizing miR-7 suppresses B cell hyperresponsiveness and inhibits lupus development. J Autoimmun. 2020;109:102440. https://doi.org/10.1016/j.jaut.2020.102440.

    Article  CAS  PubMed  Google Scholar 

  112. Yildirim-Toruner C, Diamond B. Current and novel therapeutics in the treatment of systemic lupus erythematosus. J Allergy Clin Immunol. 2011;127:303–12. https://doi.org/10.1016/j.jaci.2010.12.1087.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors acknowledge Jaypee Institute of Information Technology, Noida, for all the support provided.

Funding

None.

Author information

Authors and Affiliations

  1. Department of Biotechnology, A 10, Jaypee Institute of Information Technology, Sector-62, Noida, Uttar Pradesh, 201309, India

    Urshila Naithani, Priyanjal Jain, Aastha Sachan, Prachi Khare & Reema Gabrani

Authors
  1. Urshila Naithani
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Priyanjal Jain
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Aastha Sachan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Prachi Khare
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Reema Gabrani
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

UN, PJ, AS, and PK wrote different aspects of the main manuscript text and prepared tables and figures; RG contributed to conceptualization and reviewing of the manuscript.

Corresponding author

Correspondence to Reema Gabrani.

Ethics declarations

Conflict of interest

No potential conflict of interest has been reported by the authors.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent for publication

All authors have given consent for publication.

Additional information

Publisher's Note

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

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Naithani, U., Jain, P., Sachan, A. et al. MicroRNA as a potential biomarker for systemic lupus erythematosus: pathogenesis and targeted therapy. Clin Exp Med 23, 4065–4077 (2023). https://doi.org/10.1007/s10238-023-01234-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10238-023-01234-7

Keywords

Search

Navigation