title: Altered microRNA expression profile with miR-146a upregulation in CD4+ T cells from patients with rheumatoid arthritis.
abstract: BACKGROUND
  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.
authors.affiliation: Institute of Immunology, PLA, Third Military Medical University, 30# Gaotanyan Street, District Shipingba, Chongqing 400038, PR China.
authors.forename: Jingyi
authors.initials: J
authors.lastname: Li
authors.forename: Ying
authors.initials: Y
authors.lastname: Wan
authors.forename: Qiuye
authors.initials: Q
authors.lastname: Guo
authors.forename: Liyun
authors.initials: L
authors.lastname: Zou
authors.forename: Jinyu
authors.initials: J
authors.lastname: Zhang
authors.forename: Yongfei
authors.initials: Y
authors.lastname: Fang
authors.forename: Jingbo
authors.initials: J
authors.lastname: Zhang
authors.forename: Jinjun
authors.initials: J
authors.lastname: Zhang
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Fu
authors.forename: Hongli
authors.initials: H
authors.lastname: Liu
authors.forename: Liwei
authors.initials: L
authors.lastname: Lu
authors.forename: Yuzhang
authors.initials: Y
authors.lastname: Wu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000328:Adult; D017209:Apoptosis / Q000502:physiology; D051017:Apoptosis Regulatory Proteins; D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D013582:Synovial Fluid / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D015415:Biomarkers; C490780:FAF1 protein, human; C542542:MIRN146 microRNA, human; C574861:MIRN363 microRNA, human; D035683:MicroRNAs; D014409:Tumor Necrosis Factor-alpha
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