MicroRNA-663 activates the canonical Wnt signaling through the adenomatous polyposis coli suppression.
Immunol Lett
; 166(1): 45-54, 2015 Jul.
Article
em En
| MEDLINE
| ID: mdl-26028359
ABSTRACT
Rheumatoid arthritis (RA) is a symmetrical polyarticular autoimmune disease of unknown etiology. In this present study, we observed that the adenomatous polyposis coli (APC) expression is down-regulated and the expression of microRNA (miR)-663 increased significantly in synovium from RA patients compared with control. Target gene prediction for miR-663 revealed that the mRNA of APC gene, which is a member of the canonical Wnt signaling pathway, has a miR-663 binding site in its 3'-untranslated region (3'UTR). The result showed that increased miR-663 suppressed the APC expression significantly, and this down-regulation of APC expression triggered the activation of canonical Wnt signaling through accumulation of ß-catenin in fibroblast-like synoviocytes (FLS). In addition, increased miR-663 induced the FLS proliferation and the expression MMP3 and fibronectin during disease development. Therefore, miR-663 can be considered as a critical regulator of RA pathogenesis and can be utilized for developing miRNA-based therapeutic agents for RA patients.
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Base de dados:
MEDLINE
Assunto principal:
Artrite Reumatoide
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Membrana Sinovial
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Proteína da Polipose Adenomatosa do Colo
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MicroRNAs
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Via de Sinalização Wnt
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article