Gaceta Médica de México

Contents by Year, Volume and Issue

Table of Contents

General Information

Instructions for Authors

Message to Editor

Editorial Board

>Journals >Gaceta Médica de México >Year 2019, Issue 1

Alemán-Ávila I, Cadena-Sandoval D, Jiménez MM, Ramírez-Bello J
MicroRNA en enfermedades autoinmunes
Gac Med Mex 2019; 155 (1)

Language: Español
References: 54
Page: 63-71
PDF: 1270.41 Kb.

Full text


MicroRNAs (miRNAs) are small non-coding RNAs of approximately 17-24 nucleotides in length, which complementarily and mainly bind in 3’ UTR (untranslated region) regions of different messenger RNAs (mRNAs). Their general function is to negatively regulate gene expression at the posttranscriptional level, thus inhibiting translation. miRNA abnormal expression profiles of have been found in different human fluids, cells and tissues affected by different autoimmune diseases, and some of them have been proposed as potential biomarkers of diagnosis, prognosis, activity etc. in these pathologies. In addition, common variants of the human genome, called single-nucleotide polymorphisms (SNPs), located within miRNA genes, have been associated with susceptibility, severity and activity in these diseases. The purpose of this review is to describe miRNA biogenesis and function, as well as the expression profiles and SNPs in miRNA genes that are associated with different autoimmune diseases, including autoimmune thyroiditis (Hashimoto’s thyroiditis and Graves’ disease), systemic lupus erythematosus, rheumatoid arthritis and primary Sjögren’s syndrome.

Key words: MicroRNA, Inflammation, Autoimmunity, Gene expression, Single-nucleotide polymorphisms.


  1. Mendell JT. MicroRNAs: critical regulators of development, cellular physiology and malignancy. Cell Cycle. 2005;4:1179-1184.

  2. Ambros V. The functions of animal microRNAs. Nature. 2004;431:350-355.

  3. Bernecker C, Lenz L, Ostapczuk MS, Schinner S, Willenberg H, Ehlers M, et al. MicroRNAs miR-146a1, miR-155 2, and miR-200a1 are regulated in autoimmune thyroid diseases. Thyroid. 2012;22:1294-1295.

  4. Baltimore D, Boldin MP, O’Connell RM, Rao DS, Taganov KD. MicroRNAs: new regulators of immune cell development and function. Nat Immunol. 2008;9 839-845.

  5. O’Connell RM, Rao DS, Chaudhuri AA, Baltimore D. Physiological and pathological roles for microRNAs in the immune system. Nat Rev Immunol. 2010;10:111-122.

  6. Li K, Du Y, Jiang BL, He JF. Increased microRNA-155 and decreased microRNA-146a may promote ocular inflammation and proliferation in Graves’ ophthalmopathy. Med Sci Monit. 2014;20 639-643.

  7. Liu X, Han Z, Yang C. Associations of microRNA single nucleotide polymorphisms and disease risk and pathophysiology. Clin Genet. 2016;92:235-242.

  8. Chatzikyriakidou A, Voulgari PV, Georgiou I, Drosos AA. miRNA and related polymorphisms in rheumatoid arthritis susceptibility. Autoimmun Rev. 2012;11:636-641.

  9. Alevizos I, Illei GG. MicroRNAs as biomarkers in rheumatic diseases. Nat Rev Rheumatol. 2010;6 391-398.

  10. Chen JQ, Papp G, Szodoray P, Zeher M. The role of microRNAs in the pathogenesis of autoimmune diseases. Autoimmun Rev. 2016;15: 1171-1180.

  11. 11- Marques-Rocha JL, Samblas M, Milagro FI, Bressan J, Martínez JA, Marti A. Noncoding RNAs, cytokines, and inflammation-related diseases. FASEB J. 2015;29:3595-3611.

  12. UI Hussain M. Micro-RNAs (miRNA): genomic organisation, biogenesis and mode of action. Cell Tissue Res. 2012;349:405-413.

  13. Bohnsack MT, Czaplinski K, Gorlich D. Exportin 5 is a RanGTP-dependent dsRNA-binding protein that mediates nuclear export of pre-miRNA. RNA. 2004;10:185-191.

  14. Cannell IG, Kong YW, Bushell M. How do microRNAs regulate gene expression? Biochem Soc Trans. 2008;36:1224-1231.

  15. Mohr AM, Mott JL. Overview of microRNA biology. Semin Liver Dis. 2015;35:3-11.

  16. Lee HM, Kim TS, Jo EK. MiR-146 and miR-125 in the regulation of innate immunity and inflammation. BMB Rep. 2016;49:311-318.

  17. 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;60:1065-1075.

  18. Boldin MP, Taganov KD, Rao DS, Yang L, Zhao JL, Kalwani M, et al. miR-146a is a significant brake on autoimmunity, myeloproliferation, and cancer in mice. J Exp Med. 2011;208:1189-1201.

  19. Garo LP, Murugaiyan G. Contribution of microRNAs to autoimmune diseases. Cell Mol Life Sci. 2016;73:2041-2051.

  20. Cobb BS, Nesterova TB, Thompson E, Hertweck A, O’Connor E, Godwin J, et al. T cell lineage choice and differentiation in the absence of RNase III enzyme Dicer. J Exp Med. 2005;201:1367-1373.

  21. González-Martín A, Adams BD, Lai M, Shepherd J, Salvador-Bernaldez M, Salvador JM, et al. The microRNA miR-148a functions as a critical regulator of B cell tolerance and autoimmunity. Nat Immunol. 2016;17: 433-440.

  22. Ramírez-Bello J, Jiménez-Morales S. Implicaciones funcionales de los polimorfismos (SNP) en genes codificantes de proteínas y no codificantes en enfermedades multifactoriales. Gac Med Mex. 2017;153 238-250.

  23. Rodríguez-Elías AK, Maldonado-Murillo K, López-Mendoza LF, Ramírez- Bello J. Genetics and genomics in rheumatoid arthritis (RA): an update. Gac Med Mex. 2016;152:218-227.

  24. Brown RS. Autoimmune thyroid disease: unlocking a complex puzzle. Curr Opin Pediatr. 2009;21:523-528.

  25. Burch HB, Cooper DS. Management of Graves disease: a review. JAMA. 2015;314:2544-2554.

  26. Yamada H, Itoh M, Hiratsuka I, Hashimoto S. Circulating microRNAs in autoimmune thyroid diseases. Clin Endocrinol (Oxf). 2014;81:276-281.

  27. Li T, Morgan MJ, Choksi S, Zhang Y, Kim YS, Liu ZG. MicroRNAs modulate the noncanonical transcription factor NF-kappaB pathway by regulating expression of the kinase IKKalpha during macrophage differentiation. Nat Immunol. 2010;11:799-805.

  28. Liu R, Ma X, Xu L, Wang D, Jiang X, Zhu W, et al. Differential microRNA expression in peripheral blood mononuclear cells from Graves’ disease patients. J Clin Endocrinol Metab. 2012;97:E968-E972.

  29. Hiratsuka I, Yamada H, Munetsuna E, Hashimoto S, Itoh M. Circulating microRNAs in Graves’ disease in relation to clinical activity. Thyroid. 2016;26:1431-1440.

  30. Cai T, Li J, An X, Yan N, Li D, Jiang Y, et al. Polymorphisms in MIR499a and MIR125a gene are associated with autoimmune thyroid diseases. Mol Cell Endocrinol. 2017;440:106-115.

  31. Singh RP, Hasan S, Sharma S, Nagla S, Yamaguchi DT, Wong DT, et al. Th17 cells in inflammation and autoimmunity. Autoimmun Rev. 2014;13:1174-1181.

  32. Inoue Y, Watanabe M, Inoue N, Kagawa T, Shibutani S, Otsu H, et al. Associations of single nucleotide polymorphisms in precursor-microRNA (miR)-125a and the expression of mature miR-125a with the development and prognosis of autoimmune thyroid diseases. Clin Exp Immunol. 2014;178 229-235.

  33. Pyzik A, Grywalska E, Matyjaszek-Matuszek B, Roliński J. Immune disorders in Hashimoto’s thyroiditis: what do we know so far? J Immunol Res. 2015;2015:979167.

  34. Kagawa T, Watanabe M, Inoue N, Otsu H, Saeki M, Katsumata Y, et al. Increases of microRNA let-7e in peripheral blood mononuclear cells in Hashimoto’s disease. Endocr J. 2016;63:375-380.

  35. Peng H, Liu Y, Tian J, Ma J, Tang X, Yang J, et al. Decreased expression of microRNA-125a-3p upregulates interleukin-23 receptor in patients with Hashimoto’s thyroiditis. Immunol Res. 2015;62:129-136.

  36. Zan H, Tat C, Casali P. MicroRNA in lupus. Autoimmunity. 2014;47: 272-285.

  37. Yan S, Yim LY, Lu L, Lau CS, Chan VS. MicroRNA regulation in systemic lupus erythematosus pathogenesis. Immune Netw. 2014;14:138-148.

  38. 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 cell by directly and indirectly targeting DNA methyltransferase 1. J Immunol. 2010;184 6773-6781.

  39. Tang ZM, Fang M, Wang JP, Cai PC, Wang P, Hu LH. Clinical relevance of plasma miR-21 in new-onset systemic lupus erythematosus patients. J Clin Lab Anal. 2014;28:446-451.

  40. Husakova M. MicroRNAs in the key events of systemic lupus erythematosus pathogenesis. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2016;160:327-342.

  41. Rasmussen TK, Andersen T, Bak RO, Yiu G, Sørensen CM, Stengaard- Pedersen K, et al. Overexpression of microRNA-155 increases IL-21 mediated STAT3 signaling and IL-21 production in systemic lupus erythematosus. Arthritis Res Ther. 2015;17:154.

  42. Lee YH, Bae SC. The miR-146a polymorphism and susceptibility to systemic lupus erythematosus and rheumatoid arthritis: a meta-analysis. Z Rheumatol. 2015;74:153-156.

  43. Fu L, Jin L, Yan L, Shi J, Wang H, Zhou B, et al. Comprehensive review of genetic association studies and meta-analysis on miRNA polymorphisms and rheumatoid arthritis and systemic lupus erythematosus susceptibility. Hum Immunol. 2016;77:1-6.

  44. Murata K, Furu M, Yoshitomi H, Ishikawa M, Shibuya H, Hashimoto M, et al. Comprehensive microRNA analysis identifies miR-24 and miR- 125a-5p as plasma biomarkers for rheumatoid arthritis. PLoS One. 2013;8:e69118.

  45. Churov AV, Oleinik EK, Knip M. MicroRNAs in rheumatoid arthritis: altered expression and diagnostic potential. Autoimmun Rev. 2015;14:1029-1037.

  46. 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;60:1294-1304.

  47. Yang S, Yang Y. Downregulation of microRNA-221 decreases migration and invasion in fibroblast-like synoviocytes in rheumatoid arthritis. Mol Med Rep. 2015;12:2395-2401.

  48. Hashemi M, Eskandari-Nasab E, Zakeri Z, Atabaki M, Bahari G, Jahantigh M, et al. Association of pre-miRNA-146a rs2910164 and pre-miR-499 rs3746444 polymorphisms and susceptibility to rheumatoid arthritis. Mol Med Rep. 2013;7:287-291.

  49. Toraih EA, Ismail NM, Toraih AA, Hussein MH, Fawzy MS. Precursor miR- 499a variant but not miR-196a2 is associated with rheumatoid arthritis susceptibility in an Egyptian population. Mol Diagn Ther. 2016;20:279-295.

  50. Alevizos I, Illei GG. MicroRNAs in Sjögren’s syndrome as a prototypic autoimmune disease. Autoimmun Rev. 2010;9:618-621.

  51. Zilahi E, Tarr T, Papp G, Griger Z, Sipka S, Zeher M. Increased microRNA- 146a/b, TRAF6 gene and decreased IRAK1 gene expressions in the peripheral mononuclear cells of patients with Sjögren’s syndrome. Immunol Lett. 2012;141:165-168.

  52. Pauley KM, Stewart CM, Gauna AE, Dupre LC, Kuklani R, Chan AL, et al. Altered miR‐146a expression in Sjögren’s syndrome and its functional role in innate immunity. Eur J Immunol. 2011;41:2029-2039.

  53. Gourzi VC, Kapsogeorgou EK, Kyriakidis NC, Tzioufas AG. Study of microRNAs (miRNA) that are predicted to target the autoantigens Ro/ SSA and La/SSB in primary Sjögren’s Syndrome. Clin Exp Immunol. 2015;182:14-22.

  54. Chen JQ, Papp G, Póliska S, Azabó K, Tarr T, Bálint BL, et al. MicroRNA expression profiles identify disease-specific alterations in systemic lupus erythematosus and primary Sjögren’s syndrome. PLoS One. 2017;12:e0174585.

>Journals >Gaceta Médica de México >Year 2019, Issue 1

· Journal Index 
· Links 

Copyright 2019