Dysregulated microRNA expression in rheumatoid arthritis families—a comparison between rheumatoid arthritis patients, their first-degree relatives, and healthy controls

Abstract

Objective Recent studies have demonstrated an altered expression of certain microRNAs in patients with rheumatoid arthritis (RA) as well as their first-degree relatives (FDRs) compared to healthy controls (HCs), suggesting a role of microRNA in the progression of the disease. To corroborate this, a set of well-characterized RA families originating from northern Sweden were analyzed for differential expression of a selected set of microRNAs. Method MicroRNA was isolated from frozen peripheral blood cells obtained from 21 different families and included 26 RA patients, 22 FDRs, and 21 HCs. Expression of the selected microRNAs miR-22-3p, miR-26b-5p, miR-34a-3p, miR-103a-3p, miR-142-3p, miR-146a-5p, miR-155, miR-346, and miR-451a was determined by a two-step quantitative real-time polymerase chain reaction (qRT-PCR). Statistical analysis including clinical variables was applied. Results Out of the nine selected microRNAs that previously have been linked to RA, we confirmed four after adjusting for age and gender, i.e., miR-22-3p (p = 0.020), miR-26b-5p (p = 0.018), miR-142-3p (p = 0.005), and miR-155 (p = 0.033). Moreover, a significant trend with an intermediate microRNA expression in FDR was observed for the same four microRNAs. In addition, analysis of the effect of corticosteroid use showed modulation of miR-103a-3p expression. Conclusions We confirm that microRNAs seem to be involved in the development of RA, and that the expression pattern in FDR is partly overlapping with RA patients. The contribution of single microRNAs in relation to the complex network including all microRNAs and other molecules is still to be revealed. Key Points• Expression levels of miR-22-3p, miR-26b-5p, miR-142-3p, and miR-155 were significantly altered in RA patients compared to those in controls.• In first-degree relatives, a significant trend with an intermediate microRNA expression in FDR was observed for the same four microRNAs.

Rheumatoid arthritis fibroblast-like synoviocytes maintain tumor-like biological characteristics through ciRS-7-dependent regulation of miR-7

“…Previously reported miRNAs in RA-FLS were predicted from mRNAs based on various bioinformational platform, and these mRNAs were not analyzed at a Weighted Correlation Network Analysis (WGCNA). There are numerous miRNAs can be further investigated in RA-FLS's biological characteristics (6)(7)(8). To further identify the miRNAs in RA-FLS, we performed miRNA and mRNA-sequencing on FLS from 3 RA patients, FLS from 3 trauma patients as the control.…”

Pathogenesis of rheumatoid arthritis: one year in review 2022

“…Among the sncRNAs, micro-RNAs (miRNAs) can regulate gene expression mainly through combining with the 3́untranslated regions (3́UTRs) of target messenger RNA (mRNA). Altered expression levels of a number of miRNAs, including miR-22-3p, miR-26b-5p, miR-142-3p, and miR-155 have been also confirmed in RA patients (19). Moreover, serum expression of miR-224, miR-760, miR-483-5p, miR-378 and miR-375 was found to be significantly upregulated and it seems to correlate with the DAS28 score in RA patients (20), while miR-NA-22 appears to be associated with disease activity in well-established RA (21).…”

Research progress on microRNA in gout

“…MiR-142-3p is located on human chromosome 17 and can play an important role as an anti-inflammatory or proinflammatory gene in inflammation-related diseases ( Hu and Wang, 2016 ; Zhang et al, 2020a ). For example, miR-142-3p is involved in the regulation of OA ( Gao et al, 2019 ), rheumatoid arthritis (RA) ( Renman et al, 2021 ) and GA ( Bohatá et al, 2021 ). Wang et al (2016) found that the expression of miR-142-3p was reduced in mice with OA and had a targeted regulatory role with high mobility group box 1 (HMGB1).…”

“…Upregulation of miR-142-3p expression inhibited chondrocyte apoptosis and inflammation. MiR-142-3p was also found to be aberrantly expressed in RA patients compared to healthy controls ( Renman et al, 2021 ). Most recently, Bohatá et al (2021) detected the expression of miR-142-3p in the plasma of normal uric acid controls, hyperuricemia and gout patients, and the results showed that the expression of miR-142-3p was upregulated in hyperuricemia and gout patients.…”