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

File Download Links for fulltext
(May Require Subscription)
Supplementary

  • Basic View
  • Metadata View
  • XML View
TitleAltered microRNA expression profile with miR-146a upregulation in CD4 + T cells from patients with rheumatoid arthritis
AuthorsLi, J2
Wan, Y2
Guo, Q2
Zou, L2
Zhang, J2
Fang, Y2
Zhang, J2
Zhang, J2
Fu, X2
Liu, H2
Lu, L1
Wu, Y2
Issue Date2010
PublisherBioMed Central Ltd. The Journal's web site is located at http://arthritis-research.com/
CitationArthritis Research And Therapy, 2010, v. 12 n. 3 [How to Cite?]
DOI: http://dx.doi.org/10.1186/ar3006
AbstractIntroduction: 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-α), and in vitro studies showed TNF-α 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-α 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. © 2010 Li et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
ISSN1478-6354
2011 Impact Factor: 4.445
2011 SCImago Journal Rankings: 0.482
DOIhttp://dx.doi.org/10.1186/ar3006
PubMed Central IDPMC2911863
ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorLi, J
dc.contributor.authorWan, Y
dc.contributor.authorGuo, Q
dc.contributor.authorZou, L
dc.contributor.authorZhang, J
dc.contributor.authorFang, Y
dc.contributor.authorZhang, J
dc.contributor.authorZhang, J
dc.contributor.authorFu, X
dc.contributor.authorLiu, H
dc.contributor.authorLu, L
dc.contributor.authorWu, Y
dc.date.accessioned2010-12-23T08:38:31Z
dc.date.available2010-12-23T08:38:31Z
dc.date.issued2010
dc.description.abstractIntroduction: 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-α), and in vitro studies showed TNF-α 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-α 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. © 2010 Li et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
dc.description.naturepublished_or_final_version
dc.identifier.citationArthritis Research And Therapy, 2010, v. 12 n. 3 [How to Cite?]
DOI: http://dx.doi.org/10.1186/ar3006
dc.identifier.citeulike7163455
dc.identifier.doihttp://dx.doi.org/10.1186/ar3006
dc.identifier.hkuros176950
dc.identifier.isiWOS:000280227900026
Funding AgencyGrant Number
National Basic Research Program of China (973 program)2007CB512401
2010CB529100
National Natural Science Foundation of China30801030
30871224
Funding Information:

We thank Dr. D. Baltimore for providing the lentiviral vector FUGW. We also thank Dr. S.J. Elledge for providing plasmid pPRIME-CMV-GFP-FF3. We would like to express our gratitude to Bao Zhang for technical assistance. We are grateful to Drs. Lili Du, Yanjie Zhang and Bo Zhu for critical reading of the manuscript. This study was supported by grants from the National Basic Research Program of China (973 program, No. 2007CB512401, 2010CB529100) and the National Natural Science Foundation of China (No. 30801030, 30871224).

dc.identifier.issn1478-6354
2011 Impact Factor: 4.445
2011 SCImago Journal Rankings: 0.482
dc.identifier.issue3
dc.identifier.openurl
dc.identifier.pmcidPMC2911863
dc.identifier.pmid20459811
dc.identifier.scopuseid_2-s2.0-77951973193
dc.identifier.urihttp://hdl.handle.net/10722/129533
dc.identifier.volume12
dc.languageeng
dc.publisherBioMed Central Ltd. The Journal's web site is located at http://arthritis-research.com/
dc.publisher.placeUnited Kingdom
dc.relation.ispartofArthritis Research and Therapy
dc.relation.referencesReferences in Scopus
dc.rightsArthritis Research & Therapy. Copyright © BioMed Central Ltd.
dc.subject.meshAdaptor Proteins, Signal Transducing - metabolism
dc.subject.meshArthritis, Rheumatoid - metabolism - pathology
dc.subject.meshCD4-Positive T-Lymphocytes - metabolism - pathology
dc.subject.meshMicroRNAs - metabolism
dc.subject.meshUp-Regulation - physiology
dc.titleAltered microRNA expression profile with miR-146a upregulation in CD4 + T cells from patients with rheumatoid arthritis
dc.typeArticle
Author Affiliations
  1. The University of Hong Kong
  2. Third Military Medical University