Abstract
MicroRNAs are short endogenous non-coding RNAs that regulate gene expression in various physiological and pathological conditions. To characterize autoantigen-targeting microRNAs in Sjögren’s syndrome (SS), a systematic study was carried out, in which a candidate microRNA set was first identified by bioinformatics analysis and literature search. Then, their gene silencing activities were evaluated with fusion reporter gene and endogenous targets, leading to the identification of three microRNAs: TRIM21-targeting miR-1207-5p, TRIM21-targeting miR-4695-3p, and La autoantigen-targeting miR-299-5p. Compared to healthy controls, downregulation of miR-1207-5p and miR-4695-3p expression was further revealed in the minor salivary glands of primary SS (pSS) patients. This, on the one hand, characterized two autoantigen-targeting microRNAs in Sjögren’s syndrome and, on the other hand, suggested that downregulation of miR-1207-5p and miR-4695-3p expression may lead to increased TRIM21 levels in the minor salivary glands, which contributes to the development of Sjögren’s syndrome.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Tzioufas AG, Voulgarelis M (2007) Update on Sjögren’s syndrome autoimmune epithelitis: from classification to increased neoplasias. Best Pract Res Clin Rheumatol 21:989–1010
Gabriel SE, Michaud K (2009) Epidemiological studies in incidence, prevalence, mortality, and comorbidity of the rheumatic diseases. Arthritis Res Ther 11:229. doi:10.1186/ar2669
Routsias JG, Tzioufas AG (2010) B-cell epitopes of the intracellular autoantigens Ro/SSA and La/SSB: tools to study the regulation of the autoimmune response. J Autoimmun 35:256–264
Dorner T, Feist E, Held C (1996) Differential recognition of the 52-kd Ro(SS-A) antigen by sera from patients with primary biliary cirrhosis and primary Sjögren’s syndrome. Hepatology 24:1404–1407
Routsias JG, Tzioufas AG (2007) Sjögren’s syndrome—study of autoantigens and autoantibodies. Clin Rev Allergy Immunol 32:238–251
Manoussakis MN, Kapsogeorgou EK (2010) The role of intrinsic epithelial activation in the pathogenesis of Sjögren’s syndrome. J Autoimmun 35:219–224. doi:10.1016/j.jaut.2010.06.011
Horsfall AC, Rose LM, Maini RN (1989) Autoantibody synthesis in salivary glands of Sjögren’s syndrome patients. J Autoimmun 2:559–568
Gellrich S, Rutz S, Borkowski A (1999) Analysis of V(H)-D-J(H) gene transcripts in B cells infiltrating the salivary glands and lymph node tissues of patients with Sjögren’s syndrome. Arthritis Rheum 42:240–247
Lindström FD, Eriksson P, Tejle K (1994) IgG subclasses of anti-SS-A/Ro in patients with primary Sjögren’s syndrome. Clin Immunol Immunopathol 73:358–361
Ambros V (2003) MicroRNA pathways in flies and worms: growth, death, fat, stress, and timing. Cell 113:673–676
Ambros V (2004) The functions of animal microRNAs. Nature 431(7006):350–355
Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297
Calin GA, Dumitru CD, Shimizu M (2002) Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A A99:15524–15529
Alsaleh G, Suffert G, Semaan N (2009) Bruton’s tyrosine kinase is involved in miR-346-related regulation of IL-18 release by lipopolysaccharide-activated rheumatoid fibroblast-like synoviocytes. J Immunol 182:5088–5097
Dai Y, Huang YS, Tang M (2007) Microarray analysis of microRNA expression in peripheral blood cells of systemic lupus erythematosus patients. Lupus 16:939–946
Michael A, Bajracharya SD, Yuen PS (2010) Exosomes from human saliva as a source of microRNA biomarkers. Oral Dis 16:34–38
Padgett KA, Lan RY, Leung PC (2009) Primary biliary cirrhosis is associated with altered hepatic microRNA expression. J Autoimmun 32:246–253
Pauley KM, Stewart CM, Gauna AE (2011) Altered miR-146a expression in Sjögren’s syndrome and its functional role in innate immunity. Eur J Immunol 41:2029–2039
Zilahi E, Tarr T, Papp G (2012) Increased microRNA-146a/b, TRAF6 gene and decreased IRAK1 gene expressions in the peripheral mononuclear cells of patients with Sjögren’s syndrome. Immunol Lett 141:165–168
Maurer B, Stanczyk J, Jüngel A (2010) MicroRNA-29, a key regulator of collagen expression in systemic sclerosis. Arthritis Rheum 62:1733–1743
Sonkoly E, Wei T, Janson PC (2007) MicroRNAs: novel regulators involved in the pathogenesis of psoriasis? PLoS One 2:e610
Iborra M, Bernuzzi F, Invernizzi P (2012) MicroRNAs in autoimmunity and inflammatory bowel disease: crucial regulators in immune response. Autoimmun Rev 11:305–314
Gourzi VC, Kapsogeorgou EK, Kyriakidis NC, Tzioufas AG (2015) Study of microRNAs (miRNAs) that are predicted to target the autoantigens Ro/SSA and La/SSB in primary Sjögren’s syndrome. Clin Exp Immunol 182(1):14–22
Acknowledgments
This work was supported by the Beijing Municipal Administration of Hospitals Incubating Program (PX2016065), the Nantong Jianghai Talent Program, the National High Technology Research and Development Program of China (2011AA020111), the National Science Technology Pillar Program in the 11th Five-Year Plan (2008BAI59B03), the Special Research Fund for Public Welfare and the Health Industry (201202004), and the National High-tech R&D Program of China (2012AA022501).
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Disclosures
None.
Additional information
Ying Yang and Linyi Peng contributed equally to this work.
Rights and permissions
About this article
Cite this article
Yang, Y., Peng, L., Ma, W. et al. Autoantigen-targeting microRNAs in Sjögren’s syndrome. Clin Rheumatol 35, 911–917 (2016). https://doi.org/10.1007/s10067-016-3203-3
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10067-016-3203-3