Published Apr 30, 2022

Patricia Mendes Demo  


MicroRNAs (miRNAs) are a family of non-coding single-stranded RNAs with a length of around 18-25 nucleotides that play a critical role in the control of gene expression, cell proliferation, differentiation, and apoptosis, as well as biological growth and development and illness. Autoimmune diseases are a group of disorders characterized by tissue and organ damage and resulting dysfunction as a result of autoimmune responses. Numerous studies have discovered that aberrant expression of certain miRNAs may serve as biomarkers for early detection of these diseases or as therapeutic targets. The biological properties of miRNAs and their significance in autoimmune illnesses are discussed in this review.



microRNAs, Autoimmune Diseases, Mechanisms, Diagnosis, Therapeutics

1. Ratti M, Lampis A, Ghidini M, Salati M, Mirchev MB, Valeri N, Hahne JC. MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) as new tools for cancer therapy: First steps from bench to bedside. Target Oncol 2020; 15(3):261-278. DOI: https://doi.org/10.1007/s11523-020-00717-x

2. Ying SY, Chang DC, Lin SL. The microRNA (miRNA): overview of the RNA genes that modulate gene function. Mol Biotechnol 2008; 38(3):257-268. DOI: https://doi.org/10.1007/s12033-007-9013-8

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

4. Lau PW, MacRae IJ. The molecular machines that mediate microRNA maturation. J Cell Mol Med 2009; 13(1):54-60. DOI: https://doi.org/10.1111/j.1582-4934.2008.00520.x

5. Sashital DG, Doudna JA. Structural insights into RNA interference. Curr Opin Struct Biol 2010; 20(1):90-97. DOI: https://doi.org/10.1016/j.sbi.2009.12.001

6. Shukla GC, Singh J, Barik S. MicroRNAs: Processing, maturation, target recognition and regulatory functions. Mol Cell Pharmacol 2011; 3(3):83-92.

7. Fontana L, Pelosi E, Greco P, Racanicchi S, Testa U, Liuzzi F, Croce CM, Brunetti E, Grignani F, Peschle C. MicroRNAs 17-5p-20a-106a control monocytopoiesis through AML1 targeting and M-CSF receptor upregulation. Nat Cell Biol 2007; 9(7):775-787. DOI: https://doi.org/10.1038/ncb1613

8. Alwani A, Andreasik A, Szatanek R, Siedlar M, Baj-Krzyworzeka M. The role of miRNA in regulating the fate of monocytes in health and cancer. Biomolecules 2022; 12(1):100. DOI: https://doi.org/10.3390/biom12010100

9. Yuan S, Wu Q, Wang Z, Che Y, Zheng S, Chen Y, Zhong X, Shi F. miR-223: An immune regulator in infectious disorders. Front Immunol; 12:781815. DOI: https://doi.org/10.3389/fimmu.2021.781815

10. Tahamtan A, Teymoori-Rad M, Nakstad B, Salimi V. Anti-inflammatory microRNAs and their potential for inflammatory diseases Treatment. Front Immunol 2018; 9:1377. DOI: https://doi.org/10.3389/fimmu.2018.01377

11. Zhu WD, Xu J, Zhang M, Zhu TM, Zhang YH, Sun K. MicroRNA-21 inhibits lipopolysaccharide-induced acute lung injury by targeting nuclear factor-κB. Exp Ther Med 2018; 16(6):4616-4622. DOI: https://doi.org/10.3892/etm.2018.6789

12. Wu Y, Schutt S, Paz K, Zhang M, Flynn RP, Bastian D, Sofi MH, Nguyen H, Dai M, Liu C, Chang YJ, Blazar BR, Yu XZ. MicroRNA-17-92 is required for T-cell and B-cell pathogenicity in chronic graft-versus-host disease in mice. Blood 2018; 131(17):1974-1986. DOI: https://doi.org/10.1182/blood-2017-06-789321

13. Grewers Z, Krueger A. MicroRNA miR-181-A rheostat for TCR signaling in thymic selection and peripheral T-Cell function. Int J Mol Sci 2020; 21(17):6200. DOI: https://doi.org/10.3390/ijms21176200

14. Kohlhaas S, Garden OA, Scudamore C, Turner M, Okkenhaug K, Vigorito E. Cutting edge: The Foxp3 target miR-155 contributes to the development of regulatory T cells. J Immunol 2009; 182(5):2578-2582. DOI: https://doi.org/10.4049/jimmunol.0803162

15. Pashangzadeh S, Motallebnezhad M, Vafashoar F, Khalvandi A, Mojtabavi N. Implications the role of miR-155 in the pathogenesis of autoimmune diseases. Front Immunol 2021; 12:669382. DOI: https://doi.org/10.3389/fimmu.2021.669382

16. Stahl HF, Fauti T, Ullrich N, Bopp T, Kubach J, Rust W, Labhart P, Alexiadis V, Becker C, Hafner M, Weith A, Lenter MC, Jonuleit H, Schmitt E, Mennerich D. miR-155 inhibition sensitizes CD4+ Th cells for TREG mediated suppression. PLoS One 2009; 4(9):e7158. DOI: https://doi.org/10.1371/journal.pone.0007158

17. Tesmer LA, Lundy SK, Sarkar S, Fox DA. Th17 cells in human disease. Immunol Rev 2008; 223:87-113. DOI: https://doi.org/10.1111/j.1600-065X.2008.00628.x

18. Huang J, Xu X, Yang J. miRNAs alter T Helper 17 cell fate in the pathogenesis of autoimmune diseases. Front Immunol 2021; 12:593473. DOI: https://doi.org/10.3389/fimmu.2021.593473

19. Murugaiyan G, da Cunha AP, Ajay AK, Joller N, Garo LP, Kumaradevan S, Yosef N, Vaidya VS, Weiner HL. MicroRNA-21 promotes Th17 differentiation and mediates experimental autoimmune encephalomyelitis. J Clin Invest 2015; 125(3):1069-1080. DOI: https://doi.org/10.1172/JCI74347

20. Khoshmirsafa M, Kianmehr N, Falak R, Mowla SJ, Seif F, Mirzaei B, Valizadeh M, Shekarabi M. Elevated expression of miR-21 and miR-155 in peripheral blood mononuclear cells as potential biomarkers for lupus nephritis. Int J Rheum Dis 2019; 22(3):458-467. DOI: https://doi.org/10.1111/1756-185X.13410

21. Sheedy FJ. Turning 21: Induction of miR-21 as a key switch in the inflammatory response. Front Immunol 2015; 6:19. DOI: https://doi.org/10.3389/fimmu.2015.00019

22. Garchow BG, Bartulos Encinas O, Leung YT, Tsao PY, Eisenberg RA, Caricchio R, Obad S, Petri A, Kauppinen S, Kiriakidou M. Silencing of microRNA-21 in vivo ameliorates autoimmune splenomegaly in lupus mice. EMBO Mol Med 2011; 3(10):605-615. DOI: https://doi.org/10.1002/emmm.201100171

23. Casciaro M, Di Salvo E, Brizzi T, Rodolico C, Gangemi S. Involvement of miR-126 in autoimmune disorders. Clin Mol Allergy 2018; 16:11. DOI: https://doi.org/10.1186/s12948-018-0089-4

24. Yang G, Wu D, Zeng G, Jiang O, Yuan P, Huang S, Zhu J, Tian J, Weng Y, Rao Z. Correlation between miR-126 expression and DNA hypomethylation of CD4+ T cells in rheumatoid arthritis patients. Int J Clin Exp Pathol 2015; 8(8):8929-8936.

25. Saba R, Sorensen DL, Booth SA. MicroRNA-146a: A dominant, negative regulator of the innate immune response. Front Immunol 2014; 5:578. DOI: https://doi.org/10.3389/fimmu.2014.00578

26. Chi M, Ma K, Li Y, Quan M, Han Z, Ding Z, Liang X, Zhang Q, Song L, Liu C. Immunological involvement of microRNAs in the key events of systemic lupus erythematosus. Front Immunol 2021; 12:699684. DOI: https://doi.org/10.3389/fimmu.2021.699684

27. Ceribelli A, Yao B, Dominguez-Gutierrez PR, Chan EK. Lupus T cells switched on by DNA hypomethylation via microRNA? Arthritis Rheum 2011; 63(5):1177-1181. DOI: https://doi.org/10.1002/art.30192

28. Hughes T, Sawalha AH. The role of epigenetic variation in the pathogenesis of systemic lupus erythematosus. Arthritis Res Ther 2011; 13(5):245. DOI: https://doi.org/10.1186/ar3484

29. Qu B, Shen N. miRNAs in the pathogenesis of systemic lupus erythematosus. Int J Mol Sci 2015; 16(5):9557-9572. DOI: https://doi.org/10.3390/ijms16059557

30. Chan EK, Satoh M, Pauley KM. Contrast in aberrant microRNA expression in systemic lupus erythematosus and rheumatoid arthritis: Is microRNA-146 all we need? Arthritis Rheum 2009; 60(4):912-915. DOI: https://doi.org/10.1002/art.24421

31. So BYF, Yap DYH, Chan TM. MicroRNAs in lupus nephritis-role in disease pathogenesis and clinical applications. Int J Mol Sci 2021 Oct 4; 22(19):10737. DOI: https://doi.org/10.3390/ijms221910737

32. Bagheri-Hosseinabadi Z, Mirzaei MR, Hajizadeh MR, Asadi F, Rezaeian M, Abbasifard M. Plasma microRNAs (miR-146a, miR-103a, and miR-155) as potential biomarkers for rheumatoid arthritis (RA) and disease activity in Iranian patients. Mediterr J Rheumatol 2021; 32(4):324-330. DOI: https://doi.org/10.31138/mjr.32.4.324

33. Kriegsmann M, Randau TM, Gravius S, Lisenko K, Altmann C, Arens N, Kriegsmann J. Expression of miR-146a, miR-155, and miR-223 in formalin-fixed paraffin-embedded synovial tissues of patients with rheumatoid arthritis and osteoarthritis. Virchows Arch 2016; 469(1):93-100. DOI: https://doi.org/10.1007/s00428-016-1939-4

34. Nakasa T, Miyaki S, Okubo A, Hashimoto M, Nishida K, Ochi M, Asahara H. Expression of microRNA-146 in rheumatoid arthritis synovial tissue. Arthritis Rheum 2008; 58(5):1284-1292. DOI: https://doi.org/10.1002/art.23429

35. Niimoto T, Nakasa T, Ishikawa M, Okuhara A, Izumi B, Deie M, Suzuki O, Adachi N, Ochi M. MicroRNA-146a expresses in interleukin-17 producing T cells in rheumatoid arthritis patients. BMC Musculoskelet Disord 2010; 11:209. DOI: https://doi.org/10.1186/1471-2474-11-209

36. Kurowska-Stolarska M, Alivernini S, Ballantine LE, Asquith DL, Millar NL, Gilchrist DS, Reilly J, Ierna M, Fraser AR, Stolarski B, McSharry C, Hueber AJ, Baxter D, Hunter J, Gay S, Liew FY, McInnes IB. MicroRNA-155 as a proinflammatory regulator in clinical and experimental arthritis. Proc Natl Acad Sci USA 2011; 108(27):11193-11198. DOI: https://doi.org/10.1073/pnas.1019536108

37. Wang Y, Feng T, Duan S, Shi Y, Li S, Zhang X, Zhang L. miR-155 promotes fibroblast-like synoviocyte proliferation and inflammatory cytokine secretion in rheumatoid arthritis by targeting FOXO3a. Exp Ther Med 2020; 19(2):1288-1296. DOI: https://doi.org/10.3892/etm.2019.8330

38. Hassine HB, Boumiza A, Sghiri R, Baccouche K, Boussaid I, Atig A, Shakoor Z, Bouajina E, Zemni R. Micro RNA-146a but not IRAK1 is associated with rheumatoid arthritis in the Tunisian population. Genet Test
Mol Biomarkers 2017; 21(2):92-96. DOI: https://doi.org/10.1089/gtmb.2016.0270

39. Li J, Wan Y, Guo Q, Zou L, Zhang J, Fang Y, Zhang J, Zhang J, Fu X, Liu H, Lu L, Wu Y. Altered microRNA expression profile with miR-146a upregulation in CD4+ T cells from patients with rheumatoid arthritis. Arthritis Res Ther 2010; 12(3):R81. DOI: https://doi.org/10.1186/ar3006

40. Chen ZZ, Zhang XD, Chen Y, Wu YB. The role of circulating miR-146a in patients with rheumatoid arthritis treated by Tripterygium Wilfordii Hook F. Medicine (Baltimore) 2017; 96(20):e6775. DOI: https://doi.org/10.1097/MD.0000000000006775

41. Wang S, Wan X, Ruan Q. The MicroRNA-21 in autoimmune diseases. Int J Mol Sci 2016; 17(6):864. DOI: https://doi.org/10.3390/ijms17060864

42. Huo J, Liu T, Li F, Song X, Hou X. MicroRNA 21 5p protects melanocytes via targeting STAT3 and modulating Treg/Teff balance to alleviate vitiligo. Mol Med Rep 2021; 23(1):51. DOI: https://doi.org/10.3892/mmr.2020.11689

43. Lee GR. The Balance of Th17 versus Treg Cells in Autoimmunity. Int J Mol Sci 2018; 19(3):730. DOI: https://doi.org/10.3390/ijms19030730

44. Lu MC, Yu CL, Chen HC, Yu HC, Huang HB, Lai NS. Increased miR-223 expression in T cells from patients with rheumatoid arthritis leads to decreased insulin-like growth factor-1-mediated interleukin-10 production. Clin Exp Immunol 2014; 177(3):641-651. DOI: https://doi.org/10.1111/cei.12374

45. Tang X, Yin K, Zhu H, Tian J, Shen D, Yi L, Rui K, Ma J, Xu H, Wang S. Correlation between the expression of microRNA-301a-3p and the proportion of th17 cells in patients with rheumatoid arthritis. Inflammation 2016; 39(2):759-767. DOI: https://doi.org/10.1007/s10753-016-0304-8

46. Sawamura S, Jinnin M, Inoue K, Yamane K, Honda N, Kajihara I, Makino T, Masuguchi S, Fukushima S, Ihn H. Regulatory mechanisms of collagen expression by interleukin-22 signaling in scleroderma fibroblasts. J Dermatol Sci 2018; 90(1):52-59. DOI: https://doi.org/10.1016/j.jdermsci.2017.12.017

47. Nakamachi Y, Kawano S, Takenokuchi M, Nishimura K, Sakai Y, Chin T, Saura R, Kurosaka M, Kumagai S. 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):1294-1304. DOI: https://doi.org/10.1002/art.24475

48. Wekerle H, Lassmann H. The immunology of inflammatory demyelinating disease. McAlpine’s Multiple Sclerosis 2006; 2006:491-555. DOI: https://doi.org/10.1016/B978-0-443-07271-0.50013-6

49. Ma X, Zhou J, Zhong Y, Jiang L, Mu P, Li Y, Singh N, Nagarkatti M, Nagarkatti P. Expression, regulation and function of microRNAs in multiple sclerosis. Int J Med Sci 2014; 11(8):810-818. DOI: https://doi.org/10.7150/ijms.8647

50. Murugaiyan G, da Cunha AP, Ajay AK, Joller N, Garo LP, Kumaradevan S, Yosef N, Vaidya VS, Weiner HL. MicroRNA-21 promotes Th17 differentiation and mediates experimental autoimmune encephalomyelitis. J Clin Invest 2015; 125(3):1069-1080. DOI: https://doi.org/10.1172/JCI74347

51. Chen C, Zhou Y, Wang J, Yan Y, Peng L, Qiu W. Dysregulated microRNA involvement in multiple sclerosis by induction of T Helper 17 cell differentiation. Front Immunol 2018; 9:1256. DOI: https://doi.org/10.3389/fimmu.2018.01256

52. Seddiki N, Brezar V, Ruffin N, Lévy Y, Swaminathan S. Role of miR-155 in the regulation of lymphocyte immune function and disease. Immunology 2014; 142(1):32-38. DOI: https://doi.org/10.1111/imm.12227

53. Escobar TM, Kanellopoulou C, Kugler DG, Kilaru G, Nguyen CK, Nagarajan V, Bhairavabhotla RK, Northrup D, Zahr R, Burr P, Liu X, Zhao K, Sher A, Jankovic D, Zhu J, Muljo SA. miR-155 activates cytokine gene expression in Th17 cells by regulating the DNA-binding protein Jarid2 to relieve polycomb-mediated repression. Immunity 2014; 40(6):865-879. DOI: https://doi.org/10.1016/j.immuni.2014.03.014

54. Wei B, Pei G. microRNAs: Critical regulators in Th17 cells and players in diseases. Cell Mol Immunol 2010; 7(3):175-181. DOI: https://doi.org/10.1038/cmi.2010.19

55. de Faria O Jr, Moore CS, Kennedy TE, Antel JP, Bar-Or A, Dhaunchak AS. MicroRNA dysregulation in multiple sclerosis. Front Genet 2013; 3:311. DOI: https://doi.org/10.3389/fgene.2012.00311. Erratum in: Front Genet 2013; 4:90.

56. Wang H. MicroRNAs, Multiple sclerosis, and depression. Int J Mol Sci 2021; 22(15):7802. DOI: https://doi.org/10.3390/ijms22157802

57. Elkhodiry AA, El Tayebi HM. Scavenging the hidden impacts of non-coding RNAs in multiple sclerosis. Noncoding RNA Res 2021; 6(4):187-199. DOI: https://doi.org/10.1016/j.ncrna.2021.12.002

58. Goody RJ, Beckham JD, Rubtsova K, Tyler KL. JAK-STAT signaling pathways are activated in the brain following reovirus infection. J Neurovirol 2007; 13(4):373-383. DOI: https://doi.org/10.1080/13550280701344983

59. Otaegui D, Baranzini SE, Armañanzas R, Calvo B, Muñoz-Culla M, Khankhanian P, Inza I, Lozano JA, Castillo-Triviño T, Asensio A, Olaskoaga J, López de Munain A. Differential micro RNA expression in PBMC from multiple sclerosis patients. PLoS One 2009; 4(7):e6309. DOI: https://doi.org/10.1371/journal.pone.0006309

60. Cui ZJ, Xie XL, Qi W, Yang YC, Bai Y, Han J, Ding Q, Jiang HQ. Cell-free miR-17-5p as a diagnostic biomarker for gastric cancer inhibits dendritic cell maturation. Onco Targets Ther 2019; 12:2661-2675. DOI: https://doi.org/10.2147/OTT.S197682

61. Cha S, Mona M, Lee KE, Kim DH, Han K. MicroRNAs in autoimmune Sjögren’s syndrome. Genomics Inform 2018; 16(4):e19. DOI: https://doi.org/10.5808/GI.2018.16.4.e19

62. Gourzi VC, Kapsogeorgou EK, Kyriakidis NC, Tzioufas AG. Study of microRNAs (miRNAs) that are predicted to target the autoantigens Ro/SSA and La/SSB in primary Sjögren’s syndrome. Clin Exp Immunol 2015; 182(1):14-22. DOI: https://doi.org/10.1111/cei.12664

63. Rady M, Watzl C, Claus M, Khorshid O, Mahran L, Abou-Aisha K. Altered expression of miR-181a and miR-146a does not change the expression of surface NCRs in human NK cells. Sci Rep 2017; 7:41381. DOI: https://doi.org/10.1038/srep41381

64. Williams AE, Choi K, Chan AL, Lee YJ, Reeves WH, Bubb MR, Stewart CM, Cha S. Sjögren’s syndrome-associated microRNAs in CD14(+) monocytes unveils targeted TGFβ signaling. Arthritis Res Ther 2016; 18(1):95. DOI: https://doi.org/10.1186/s13075-016-0987-0

65. Zhu H, Luo H, Zuo X. MicroRNAs: Their involvement in fibrosis pathogenesis and use as diagnostic biomarkers in scleroderma. Exp Mol Med 2013; 45(9):e41. DOI: https://doi.org/10.1038/emm.2013.71

66. Szabo I, Muntean L, Crisan T, Rednic V, Sirbe C, Rednic S. novel concepts in systemic sclerosis pathogenesis: Role for miRNAs. Biomedicines 2021; 9(10):1471. DOI: https://doi.org/10.3390/biomedicines9101471

67. Domingo S, Solé C, Moliné T, Ferrer B, Cortés-Hernández J. MicroRNAs in several cutaneous autoimmune diseases: Psoriasis, cutaneous lupus erythematosus and atopic dermatitis. Cells 2020; 9(12):2656. DOI: https://doi.org/10.3390/cells9122656

68. Jiao P, Wang XP, Luoreng ZM, Yang J, Jia L, Ma Y, Wei DW. miR-223: An effective regulator of immune cell differentiation and inflammation. Int J Biol Sci 2021; 17(9):2308-2322. DOI: https://doi.org/10.7150/ijbs.59876
How to Cite
Demo, P. M. (2022). The Function of MicroRNAs in Autoimmune Diseases. Science Insights, 40(5), 499–505. https://doi.org/10.15354/si.22.re033