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20459811
Altered microRNA expression profile with miR-146a upregulation in CD4+ T cells from patients with rheumatoid arthritis.

Arthritis Res Ther, 2010;12(3):R81.

Li J[1], Wan Y, Guo Q, Zou L, Zhang J, Fang Y, Zhang J, Zhang J, Fu X, Liu H, Lu L, Wu Y

Affiliations

PMID: 20459811DOI: 10.1186/ar3006

Impact factor: 5.606

Abstract
introduction: Increasing 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).
methods: The 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.
results: miRNA 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.
conclusions: We 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.
MeSH terms
Adaptor Proteins, Signal Transducing; Adult; Apoptosis; Apoptosis Regulatory Proteins; Arthritis, Rheumatoid; Biomarkers; CD4-Positive T-Lymphocytes; Case-Control Studies; Female; Humans; Linear Models; Male; MicroRNAs; Middle Aged; Synovial Fluid; Tumor Necrosis Factor-alpha; Up-Regulation
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