NDLI: MicroRNA-126 regulates DNA methylation in CD4+ T cells and contributes to systemic lupus erythematosus by targeting DNA methyltransferase 1.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Zhao, Sha Wang, Yu Liang, Yunsheng Zhao, Ming Long, Hai Ding, Shu Yin, Heng Lu, Qianjin
Description	Country affiliation: China Author Affiliation: Zhao S ( Second Xiangya Hospital and Central South University, Changsha, Hunan, China.)
Abstract	OBJECTIVE: To identify microRNA genes with abnormal expression in the CD4+ T cells of patients with systemic lupus erythematosus (SLE) and to determine the role of microRNA-126 (miR-126) in the etiology of SLE. METHODS: MicroRNA expression patterns in CD4+ T cells from patients with SLE and healthy control subjects were analyzed by microRNA microarray and stem loop quantitative polymerase chain reaction (qPCR). Luciferase reporter gene assays were performed to identify miR-126 targets. Dnmt1, CD11a, and CD70 messenger RNA and protein levels were determined by real-time qPCR, Western blotting, and flow cytometry. CD11a, CD70, and EGFL7 promoter methylation levels were detected by bisulfite sequencing. IgG levels in T cell-B cell cocultures were determined by enzyme-linked immunosorbent assay. RESULTS: The expression of 11 microRNA was significantly increased or decreased in CD4+ T cells from patients with SLE relative to that in CD4+ T cells from control subjects. Among these, miR-126 was up-regulated, and its degree of overexpression was inversely correlated with Dnmt1 protein levels. We demonstrated that miR-126 directly inhibits Dnmt1 translation via interaction with its 3'-untranslated region, and that overexpression of miR-126 in CD4+ T cells can significantly reduce Dnmt1 protein levels. The overexpression of miR-126 in CD4+ T cells from healthy donors caused the demethylation and up-regulation of genes encoding CD11a and CD70, thereby causing T cell and B cell hyperactivity. The inhibition of miR-126 in CD4+ T cells from patients with SLE had the opposite effects. Expression of the miR-126 host gene EGFL7 was also up-regulated in CD4+ T cells from patients with SLE, possibly in a hypomethylation-dependent manner. CONCLUSION: Our data suggest that miR-126 regulates DNA methylation in CD4+ T cells and contributes to T cell autoreactivity in SLE by directly targeting Dnmt1.
File Format	HTM / HTML
ISSN	00043591
e-ISSN	15290131
Journal	Arthritis & Rheumatism
Issue Number	5
Volume Number	63
Language	English
Publisher	Wiley-Blackwell
Publisher Date	2011-05-01
Publisher Place	United States
Access Restriction	Subscribed
Subject Keyword	Micrornas Research Support, Non-u.s. Gov't Cd4-positive T-lymphocytes Metabolism Reverse Transcriptase Polymerase Chain Reaction Blotting, Western Flow Cytometry Dna Methylation Lupus Erythematosus, Systemic Dna (cytosine-5-)-methyltransferase Adolescent Genetics Discipline Rheumatic Diseases
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology Pharmacology (medical) Rheumatology

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