Correlation between miR-126 expression and DNA hypomethylation of CD4+ T cells in rheumatoid arthritis patients

It has been known that the occurrence of rheumatoid arthritis (RA) was closely correlated with DNA hypomethylation in CD4+ T cells, in which DNA methyltransferase plays a certain role. This study therefore investigated the effect of miR-126 on CD4+ T cell subgroup in RA patients and the alternation...

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Bibliographic Details
Published in:International journal of clinical and experimental pathology 2015-01, Vol.8 (8), p.8929-8936
Main Authors: Yang, Ge, Wu, Daoquan, Zeng, Guang, Jiang, Ou, Yuan, Pingzong, Huang, Shenjie, Zhu, Jing, Tian, Jie, Weng, Yaguang, Rao, Zhihua
Format: Article
Language:English
Subjects:
Arthritis, Rheumatoid - genetics
Arthritis, Rheumatoid - immunology
Arthritis, Rheumatoid - metabolism
CD11a Antigen - genetics
CD11a Antigen - metabolism
CD27 Ligand - genetics
CD27 Ligand - metabolism
CD4-Positive T-Lymphocytes - metabolism
DNA (Cytosine-5-)-Methyltransferase 1
DNA (Cytosine-5-)-Methyltransferases - genetics
DNA (Cytosine-5-)-Methyltransferases - metabolism
DNA Methylation
Humans
MicroRNAs - genetics
MicroRNAs - metabolism
Original
Promoter Regions, Genetic
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Summary:It has been known that the occurrence of rheumatoid arthritis (RA) was closely correlated with DNA hypomethylation in CD4+ T cells, in which DNA methyltransferase plays a certain role. This study therefore investigated the effect of miR-126 on CD4+ T cell subgroup in RA patients and the alternation of DNA hypomethylation, in an attempt to provide new sights into the pathogenesis and treatment of RA. CD4+ T cells separated from RA patients were transfected with miRNA (miR)-126 expression vector or miR-126 inhibitor expression vector. The expression levels of CD11a, CD70 and DNMT1 mRNA were examined by real-time PCR. Protein levels of CD11a and CD70 were tested by flow cytometry while DNMT1 protein level was quantified by Western blotting. DNA was modified by sodium bisulfite and was sequenced for the methylation status of promoters of CD11a and CD70 genes. Both mRNA and protein expressions of CD11a and CD70 genes in CD4+ T cells were elevated by miR-126 transfection, along with decreased DNMT1 protein level but not mRNA level. The methylation degree of promoters of both CD11a and CD70 genes were significantly depressed after miR-126 transfection. The transfection by miR-126 inhibitor effectively reversed such effects. In RA patients, elevated miR-126 may promote the expression of CD11a and CD70 via the induction of hypomethylation of gene promoters by depressing DNMTI1 protein levels.
ISSN:1936-2625