Session 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.
V. C. Gourzi,
E. K. Kapsogeorgou,
N. C. Kyriakidis,
M. N. Manoussakis,
H. M. Moutsopoulos,
A. G. Tzioufas,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/expression-of-micrornas-mirnas-predicted-to-target-rossa-and-lassb-autoantigens-in-sjogrens-syndrome-ss/