Expression of Micrornas (miRNAs) Predicted to Target Ro/SSA and La/SSB Autoantigens in Sjögren’s Syndrome (SS)

Vasiliki C. Gourzi¹, Efstathia K. Kapsogeorgou¹, Nikolaos C. Kyriakidis¹, Menelaos N. Manoussakis¹, Haralampos M. Moutsopoulos² and Athanasios G. Tzioufas³, ¹Pathophysiology, School of Medicine, National University of Athens, Greece, Athens, Greece, ²Department of Pathophysiology, School of Medicine, University of Athens, Athens, Greece, ³Pathophysiology, School of Medicine, National University of Athens, Athens, Greece

Meeting: 2012 ACR/ARHP Annual Meeting

Keywords: Sjogren's syndrome and autoantigens

Session Information

Title: Sjögren's Syndrome - Pathogenesis

Session Type: Abstract Submissions (ACR)

Background/Purpose: microRNAs (miRNAs) are key post-transcriptional regulators of gene expression and might be implicated in the over-expression of Ro/SSA and La/SSB autoantigens in the salivary gland (SG) tissues and epithelial cells (SGEC) of SS patients. We have previously identified 11 miRNAs (let-7b, miR-16, miR-129-5p, miR-153, miR-181a, miR-200b, miR-200b*, miR-223, miR-483-5p, miR-573, miR-583) that are predicted to target the Ro/SSA (TRIM21 or TROVE2) and La/SSB mRNAs. Herein, we sought to investigate the expression of these miRNAs in SS. Therefore, we studied their expression in SG-tissues, SGECs and peripheral blood mononuclear cells (PBMC) of SS patients and sicca-complaining non-SS controls (CT), as well as their association with the expression of target mRNAs.

Methods: miRNAs and mRNAs expression of Ro52/TRIM21, Ro60/TROVE2 and La/SSB were investigated by real-time PCR in total RNA from SG-tissues, SGECs and PBMCs obtained from 27 SS patients and 22 sicca-CT. Significant differences between SS patients and CT and associations between miRNAs and mRNAs expression were evaluated by non-parametric Mann-Whitney and Spearman’s rank correlation tests, respectively.

Results: From the 11 microRNAs studied, miRs 129-5p, 153, 573 and 583 were not expressed in any of the samples studied, whereas miR-200b* was not detected in PBMCs. All others miRNAs were found to be expressed in all samples tested. Differential miRNA expression between SS and controls involved miR-16 and miR-223 in SG tissues, miR-200b in SGECs and miR-223 in PBMCs (mean±SE: 12.71±5.26 vs 2.47±0.67, p=0.05, 8671±2430 vs 3519±777, p=0.008, 2353±367 vs 1116±196.5, p=0.02 and 447200±224400 vs 50470±9577, p=0.01 in SS vs CT, respectively; Mann-Whitney analysis). miR-16 and miR-200b levels were positively associated with Ro52/TRIM21 mRNA expression (r=-0.5858, p=0.003, r=-0.4930, p=0.02 respectively) and miR-16 negatively associated with Ro60/TROVE2 mRNA expression (r=-0.4270, p=0.04) in SG-tissues. In SGECs, miR-181a expression was negatively associated with Ro52/TRIM21, whereas miR-200b with Ro60/TROVE2 mRNA expression (r=-0.3071, p=0.04, r=-0.3292, p=0.03 respectively; Spearman’s test). In addition, miR-200b* levels were positively associated with Ro52/TRIM21, Ro60/TROVE2 and La/SSB mRNA expression (r=0.3366, p=0.03, r=0.3580, p=0.02, r=0.4398, p=0.003 respectively). In PBMCs, miR-16 and miR-483-5p levels were found to positively correlate with Ro52/TRIM21 mRNA expression (r=-0.3202, p=0.05, r=-0.4698, p=0.003 respectively).

Conclusion: Our findings indicate that miR-16, miR-200b and miR-223 are deregulated in SS. Attention should be noted to the role of miR-200b in the regulation of Ro/SSA and La/SSB mRNAs. Further functional studies are now undertaken to enlighten the role of the deregulated miRNAs in disease pathogenesis and autoantigen expression.

Disclosure:

V. C. Gourzi,
None;

E. K. Kapsogeorgou,
None;

N. C. Kyriakidis,
None;

M. N. Manoussakis,
None;

H. M. Moutsopoulos,
None;

A. G. Tzioufas,
None.

« Back to 2012 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/expression-of-micrornas-mirnas-predicted-to-target-rossa-and-lassb-autoantigens-in-sjogrens-syndrome-ss/