MicroRNA Expression Analysis of Centenarians and Rheumatoid Arthritis Patients Reveals a Common Expression Pattern.
Ontology highlight
ABSTRACT:
SUBMITTER: Balzano F
PROVIDER: S-EPMC5562112 | biostudies-other | 2017
REPOSITORIES: biostudies-other
Similar Datasets
Project description:The outstanding characteristics of circulatory microRNAs (miRNAs) attract much attention in research on disease biomarkers and disease pathogenesis. This study aimed to identify the expression profiles of plasma miRNAs in patients with rheumatoid arthritis (RA). Thirty-three miRNAs were screened using an miRNA array, of which 9 miRNAs were validated as differentially expressed in the plasma of RA patients compared with healthy controls (HCs). miRNA-4634 (miR-4634), miR-181d and miR-4764-5p expression levels were increased, whereas miR-342-3p, miR-3926, miR-3925-3p, miR-122-3p, miR-9-5p and miR-219-2-3p expression levels were decreased in RA patients. The areas under the curve (AUCs) were generated to estimate the sensitivity and specificity of each miRNA or the panel of all 9 miRNAs as biomarkers for RA. AUCs for 9 individual miRNAs ranged from 0.6254 to 0.818; however, the AUC for the panel of 9 miRNAs reached 0.964. Levels of miR-122-3p, miR-3925-3p, miR-342-3p and miR-4764-5p expression showed significant differences between RA and other control groups. miR-4764-5p, miR-4634, miR-9-5p and miR-219-2-3p exhibited significant correlations with either plasma cytokine and chemokine levels or clinical features. In conclusion, this study identified 9-plasma miRNAs signature in Chinese patients with RA which may serve as noninvasive biomarkers for the diagnosis of RA.
| S-EPMC4767452 | biostudies-literature
Project description:Rheumatoid arthritis (RA) is an inflammatory autoimmune disorder; abnormal T cell immunity plays a critical role in the development of RA. Recently, A20 was identified as a key negative regulator for T cell activation and inflammatory signaling and may be involved in RA pathogenesis. In this study, we analyzed the expression level of A20, NF-κB, and A20 regulatory factor mucosa-associated lymphoid tissue lymphoma translocation gene 1 (MALT1) in patients with RA. Real-time PCR was used to determine the expression level of MALT1, MALT-V1, A20, and NF-κB genes in RA and healthy individuals (HI). Significantly lower A20 expression was found in RA patients compared with those in the healthy group, while NF-κB overexpression could be detected in patients with RA. Moreover, the MALT1 and MALT1-V1 expression level was downregulated in RA patients. A positive correlation between MALT1 and A20 and MALT1-V1 and A20 was found in patients with RA, and a tendency towards a negative correlation was found between MALT1 and NF-κB, MALT1-V1 and NF-κB, and A20 and NF-κB. In conclusion, we first characterized the alternative expression pattern of MALT1, A20, and NF-κB in RA, which may be related to abnormal T cell activation.
| S-EPMC4058209 | biostudies-literature
Project description:In osteoarthritis (OA) and rheumatoid arthritis (RA), many pathological alterations result from aberrant macrophage hyperactivation in the inflamed synovial membrane, and inhibition of macrophage effector functions is a therapeutic strategy in both diseases. Little is known, about the specific genetic circuits that are differentially deregulated in RA and OA macrophages. microRNA (miR) are short single stranded non-coding RNAs involved in the post-transcriptional regulation of gene expression. Altered expression of miRs has been described under various pathological conditions, including rheumatic and other autoimmune diseases. Here we compared the miR expression profile in macrophages isolated from OA and RA patients
2016-02-05 | GSE63745 | GEO
Project description:To validate in a cohort of 214 rheumatoid arthritis patients a panel of 10 plasmatic microRNAs, which we previously identified and that can facilitate earlier diagnosis of cardiovascular disease in rheumatoid arthritis patients. We identified 10 plasma miRs that were downregulated in male rheumatoid arthritis patients and in patients with acute myocardial infarction compared to controls suggesting that these microRNAs could be epigenetic biomarkers for cardiovascular disease in rheumatoid arthritis patients. Six of those microRNAs were validated in independent plasma samples from 214 rheumatoid arthritis patients and levels of expression were associated with surrogate markers of cardiovascular disease (carotid intima-media thickness, plaque formation, pulse wave velocity and distensibility) and with prior cardiovascular disease. Multivariate analyses adjusted for traditional confounders and treatments showed that decreased expression of microRNA-425-5p in men and decreased expression of microRNA-451 in women were significantly associated with increased (β = 0.072; p = 0.017) and decreased carotid intima-media thickness (β = -0.05; p = 0.013), respectively. MicroRNA-425-5p and microRNA-451 also increased the accuracy to discriminate patients with pathological carotid intima-media thickness by 1.8% (p = 0.036) in men and 3.5% (p = 0.027) in women, respectively. In addition, microRNA-425-5p increased the accuracy to discriminate male patients with prior cardiovascular disease by 3% (p = 0.008). Additionally, decreased expression of microRNA-451 was significantly associated with decreased pulse wave velocity (β = -0.72; p = 0.035) in overall rheumatoid arthritis population. Distensibility showed no significant association with expression levels of the microRNAs studied. We provide evidence of a possible role of microRNA-425-5p and microRNA-451 as useful epigenetic biomarkers to assess cardiovascular disease risk in patients with rheumatoid arthritis.
| S-EPMC8329234 | biostudies-literature
Project description:Rheumatoid arthritis (RA) is a complex disease with a wide range of underlying susceptibility factors. Recently, dysregulation of microRNAs (miRNAs) in RA have been reported in several immune cell types from blood. However, B cells have not been studied in detail yet. Given the autoimmune nature of RA with the presence of autoantibodies, CD19+ B cells are a key cell type in RA pathogenesis and alterations in CD19+ B cell subpopulations have been observed in patient blood. Therefore, we aimed to reveal the global miRNA repertoire and to analyze miRNA expression profile differences in homogenous RA patient phenotypes in blood-derived CD19+ B cells. Small RNA sequencing was performed on CD19+ B cells of newly diagnosed untreated RA patients (n=10), successfully methotrexate (MTX) treated RA patients in remission (MTX treated RA patients, n=18) and healthy controls (n=9). The majority of miRNAs was detected across all phenotypes. However, significant expression differences between MTX treated RA patients and controls were observed for 27 miRNAs, while no significant differences were seen between the newly diagnosed patients and controls. Several of the differentially expressed miRNAs were previously found to be dysregulated in RA including miR-223-3p, miR-486-3p and miR-23a-3p. MiRNA target enrichment analysis, using the differentially expressed miRNAs and miRNA-target interactions from miRTarBase as input, revealed enriched target genes known to play important roles in B cell activation, differentiation and B cell receptor signaling, such as STAT3, PRDM1 and PTEN. Interestingly, many of those genes showed a high degree of correlated expression in CD19+ B cells in contrast to other immune cell types. Our results suggest important regulatory functions of miRNAs in blood-derived CD19+ B cells of MTX treated RA patients and motivate for future studies investigating the interactive mechanisms between miRNA and gene targets, as well as the possible predictive power of miRNAs for RA treatment response.
| S-EPMC8062711 | biostudies-literature
Project description:In osteoarthritis (OA) and rheumatoid arthritis (RA), many pathological alterations result from aberrant macrophage hyperactivation in the inflamed synovial membrane, and inhibition of macrophage effector functions is a therapeutic strategy in both diseases. Little is known, about the specific genetic circuits that are differentially deregulated in RA and OA macrophages. microRNA (miR) are short single stranded non-coding RNAs involved in the post-transcriptional regulation of gene expression. Altered expression of miRs has been described under various pathological conditions, including rheumatic and other autoimmune diseases. Here we compared the miR expression profile in macrophages isolated from OA and RA patients miR expression in OA and RA macrophages was analyzed using Exiqon miRCURY microarrays. Three biological replicates (patients) were analyzed. Two samples (RA vs OA) were hybridized per microarray.
2016-02-05 | E-GEOD-63745 | biostudies-arrayexpress
Project description:ObjectiveRheumatoid arthritis (RA) is a common progressive autoimmune disorder that causes chronic inflammation of the joints and damage to other organs. Previous studies have reported the important role of miRNA-146a in the pathogenesis of RA. In addition, the anti-inflammatory and modulatory effects of oleuropein (OLEU) on the expression pattern of microRNAs (miRNAs) have been shown in different diseases. Therefore, this study aimed to evaluate both the sensitivity and specificity of miRNA-146a and determine the potential effects of OLEU on the expression levels of miRNA-146a and tumour necrosis factor-alpha (TNF-α) in RA patients.Materials and methodsThe participants in this experimental study were divided into 2 groups: RA (n=45) and healthy controls (n=30). The isolated peripheral blood mononuclear cells (PBMCs) were treated with different concentrations of OLEU; and the level of TNF-α expression, anti-citrullinated protein, and miRNA-146a were determined using enzyme-linked immunoassay and real-time polymerase chain reaction, respectively. In addition, the receiver operating characteristic (ROC) curve analysis evaluated the sensitivity and specificity of miRNA-146a in RA patients.ResultsResults revealed a positive correlation between the levels of miRNA-146a expression with the serum levels of C-reactive protein (CRP) and rheumatoid factor (RF) in RA patients. In addition, OLEU treatment decreased the levels of TNF-α and miRNA-146a expression in treated PBMCs samples compared with untreated cells. The ROC curve analysis showed an 85% sensitivity and 100% specificity of miRNA-146a in RA patients.ConclusionTherefore, miRNA-146a can be used as a useful biomarker for RA diagnosis, particularly for early detection. In addition, OLEU could suppress inflammation in RA patients through the regulation of miRNA-146a.
| S-EPMC10404353 | biostudies-literature
Project description:Rheumatoid arthritis (RA) is the most common autoimmune disease worldwide. Epigenetic alternations of microRNAs (miRNAs) can contribute to its pathogenesis and progression. As the first line therapy with DMARDs is not always successful, other drugs and therapeutic targets should be applied. This study aims to measure the expression level of plasma miRNAs in RA patients treated with olokizumab and to evaluate their potential as prognostic biomarkers. The expression of 9 miRNAs was quantified in 103 RA patients before treatment and at weeks 12 and 24 of olokizumab therapy by reverse transcription-polymerase chain reaction (RT-PCR) assay and analyzed in groups of responders and non-responders. Almost all miRNAs changed their expression during therapy. The ROC curve analysis of the most prominent of them together with consequent univariate and multivariate regression analysis revealed statistically significant associations with the olokizumab therapy efficiency scores for miR-26b, miR-29, miR-451, and miR-522. Therefore, these miRNAs might be a potential therapeutic response biomarker.
| S-EPMC7712090 | biostudies-literature
Project description:ObjectiveTo test the hypothesis that miR-155 regulates monocyte migratory potential via modulation of chemokine and chemokine receptor expression in RA, and thereby is associated with disease activity.MethodsThe miR-155 copy-numbers in monocytes from peripheral blood (PB) of healthy (n?=?22), RA (n?=?24) and RA SF (n?=?11) were assessed by real time-PCR using synthetic miR-155 as a quantitative standard. To evaluate the functional impact of miR-155, human monocytes were transfected with control or miR-155 mimic, and the effect on transcript levels, and production of chemokines was evaluated by Taqman low-density arrays and multiplex assays. A comparative study evaluated constitutive chemokine receptor expression in miR-155-/- and wild-type murine (CD115?+?Ly6C?+?Ly6G-) monocytes.ResultsCompared with healthy monocytes, the miR-155 copy-number was higher in RA, peripheral blood (PB) and SF monocytes (PB P?<?0.01, and SF P?<?0.0001). The miR-155 copy-number in RA PB monocytes was higher in ACPA-positive compared with ACPA-negative patients (P?=?0.033) and correlated (95% CI) with DAS28 (ESR), R?=?0.728 (0.460, 0.874), and with tender, R?=?0.631 (0.306, 0.824) and swollen, R?=?0.503 (0.125, 0.753) joint counts. Enforced-expression of miR-155 in RA monocytes stimulated the production of CCL3, CCL4, CCL5 and CCL8; upregulated CCR7 expression; and downregulated CCR2. Conversely, miR155-/- monocytes showed downregulated CCR7 and upregulated CCR2 expression.ConclusionGiven the observed correlations with disease activity, these data provide strong evidence that miR-155 can contribute to RA pathogenesis by regulating chemokine production and pro-inflammatory chemokine receptor expression, thereby promoting inflammatory cell recruitment and retention in the RA synovium.
| S-EPMC5088623 | biostudies-literature
Project description:IntroductionIncreasing evidence indicates that microRNAs (miRNAs) play a critical role in the pathogenesis of inflammatory diseases. The aim of the study was to investigate the expression pattern and function of miRNAs in CD4+ T cells from patients with rheumatoid arthritis (RA).MethodsThe expression profile of miRNAs in CD4+ T cells from synovial fluid (SF) and peripheral blood of 33 RA patients was determined by microarray assay and validated by qRT-PCR analysis. The correlation between altered expression of miRNAs and cytokine levels was determined by linear regression analysis. The role of miR-146a overexpression in regulating T cell apoptosis was evaluated by flow cytometry. A genome-wide gene expression analysis was further performed to identify miR-146a-regulated genes in T cells.ResultsmiRNA expression profile analysis revealed that miR-146a expression was significantly upregulated while miR-363 and miR-498 were downregulated in CD4+ T cells of RA patients. The level of miR-146a expression was positively correlated with levels of tumor necrosis factor-alpha (TNF-alpha), and in vitro studies showed TNF-alpha upregulated miR-146a expression in T cells. Moreover, miR-146a overexpression was found to suppress Jurkat T cell apoptosis. Finally, transcriptome analysis of miR-146a overexpression in T cells identified Fas associated factor 1 (FAF1) as a miR-146a-regulated gene, which was critically involved in modulating T cell apoptosis.ConclusionsWe have detected increased miR-146a in CD4+ T cells of RA patients and its close correlation with TNF-alpha levels. Our findings that miR-146a overexpression suppresses T cell apoptosis indicate a role of miR-146a in RA pathogenesis and provide potential novel therapeutic targets.
| S-EPMC2911863 | biostudies-literature