Moreover, the expression of miR-146adeclined significantly in serum exosomes of SLE patients compared with healthy controls. miR-146a could be internalized into MSCs via exosomes and participate in MSCs senescence through targeting TRAF6/NF-<i>κ</i>B signaling.
Interestingly, the 25 miRNAs including miR-146a, miR-16 and miR-21, which were over-expressed in pSS patients, were found to be elevated in SLE group, as well.
No association was observed in three studies with a total of 1532 cases and 2168 controls between miR-146ars2910164 and SLE risk (OR=0.911, 95% CI=0.710-1.171; CC vs. GG).
Common polymorphisms of microRNA gene MIR146A were reported as associated with different autoimmune diseases, include systemic lupus erythematosus, psoriatic arthritis, asthma and ankylosing spondylitis.
Data from this study suggest that MPA activates miR-142 and miR-146a expression through histone modification at the promoter region, which may partially explain the pharmacological mechanisms of MPA for SLE.
In addition, two studies involving 1920 SLE patients and 2472 controls were included in a meta-analysis of the association between miR-146ars2431697 SNP and SLE.
Moreover, miRNA146a expression correlates negatively to lupus activity and LN, whereas serum IFN-α has a direct correlation to both disease activity and nephritis; hence, both miRNA146a expression and serum IFN-α could be potentially important diagnostic biomarkers and potential novel strategies for therapeutic interventions, which may possibly be implied to enhance the sensitivity and specificity for the prediction of flares and prognosis in SLE patients.
A recent genome-wide association study revealed a variant (rs2431697) in an intergenic region, between the pituitary tumor-transforming 1 (PTTG1) and microRNA (miR-146a) genes, associated with systemic lupus erythematosus (SLE) susceptibility.
Studies have indicated that miR-146a is associated with the pathogenesis of several autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, and Sjögren's syndrome.
The manipulation of Ets-1 levels strongly affected miR-146a promoter activity in vitro; and the knockdown of Ets-1, mimicking its reduced expression in SLE, directly impaired the induction of miR-146a.
Further analysis showed that underexpression of miR-146a negatively correlated with clinical disease activity and with interferon (IFN) scores in patients with SLE.