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Upregulated miR-146a expression in peripheral blood mononuclear cells from rheumatoid arthritis patients
Kaleb M Pauley1, Minoru Satoh, Annie L Chan
1Department of Oral Biology, University of Florida, Gainesville, Florida 32610, USA.
Introduction:
MicroRNAs are small noncoding RNA molecules that negatively regulate gene expression via degradation or translational repression of their targeted mRNAs. It is known that aberrant microRNA expression can play important roles in cancer, but the role of microRNAs in autoimmune diseases is only beginning to emerge. In this study, the expression of selected microRNAs is examined in rheumatoid arthritis.
Methods:
Total RNA was isolated from peripheral blood mononuclear cells obtained from patients with rheumatoid arthritis, and healthy and disease control individuals, and the expression of miR-146a, miR-155, miR-132, miR-16, and microRNA let-7a was analyzed using quantitative real-time PCR.
Results:
Rheumatoid arthritis peripheral blood mononuclear cells exhibited between 1.8-fold and 2.6-fold increases in miR-146a, miR-155, miR-132, and miR-16 expression, whereas let-7a expression was not significantly different compared with healthy control individuals. In addition, two targets of miR-146a, namely tumor necrosis factor receptor-associated factor 6 (TRAF6) and IL-1 receptor-associated kinase 1 (IRAK-1), were similarly expressed between rheumatoid arthritis patients and control individuals, despite increased expression of miR-146a in patients with rheumatoid arthritis. Repression of TRAF6 and/or IRAK-1 in THP-1 cells resulted in up to an 86% reduction in tumor necrosis factor-alpha production, implicating that normal miR-146a function is critical for the regulation of tumor necrosis factor-alpha production.
Conclusions:
Recent studies have shown that synovial tissue and synovial fibroblasts from patients with rheumatoid arthritis exhibit increased expression of certain microRNAs. Our data thus demonstrate that microRNA expression in rheumatoid arthritis peripheral blood mononuclear cells mimics that of synovial tissue/fibroblasts. The increased microRNA expression in rheumatoid arthritis patients is potentially useful as a marker for disease diagnosis, progression, or treatment efficacy, but this will require confirmation using a large and well defined cohort. Our data also suggest a possible mechanism contributing to rheumatoid arthritis pathogenesis, whereby miR-146a expression is increased but unable to properly function, leading to prolonged tumor necrosis factor-alpha production in patients with rheumatoid arthritis.
Insights
MicroRNA expression is altered in rheumatoid arthritis (RA) patients, with increased miR-146a potentially contributing to disease by prolonging tumor necrosis factor-alpha production. This finding may aid in RA diagnosis and treatment.
Area of Science:
- Molecular biology
- Immunology
- Genetics
Background:
- MicroRNAs (miRNAs) are small noncoding RNAs regulating gene expression.
- Aberrant miRNA expression is implicated in cancer, with emerging roles in autoimmune diseases.
- This study investigates miRNA expression in rheumatoid arthritis (RA).
Purpose of the Study:
- To examine the expression of specific microRNAs in peripheral blood mononuclear cells (PBMCs) from RA patients.
- To investigate the functional consequence of altered miRNA expression on RA pathogenesis.
- To explore the potential of miRNAs as diagnostic or prognostic markers for RA.
Main Methods:
- Total RNA isolation from PBMCs of RA patients and controls.
- Quantitative real-time PCR analysis of miR-146a, miR-155, miR-132, miR-16, and let-7a expression.
- Analysis of miRNA targets (TRAF6, IRAK-1) and their impact on tumor necrosis factor-alpha production.
Main Results:
- RA PBMCs showed significantly increased expression of miR-146a, miR-155, miR-132, and miR-16 (1.8- to 2.6-fold).
- let-7a expression remained unchanged in RA patients compared to controls.
- Increased miR-146a correlated with reduced tumor necrosis factor-alpha production, suggesting impaired function.
Conclusions:
- miRNA expression patterns in RA PBMCs mirror those in synovial tissue.
- Altered miRNA expression, particularly miR-146a, may contribute to RA pathogenesis via dysregulated tumor necrosis factor-alpha production.
- These miRNAs could serve as potential biomarkers for RA diagnosis, progression, or treatment efficacy, pending further validation.
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