Journal
IMMUNOLOGY LETTERS
Volume 166, Issue 1, Pages 45-54Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.imlet.2015.05.011
Keywords
Rheumatoid arthritis; microRNA-663; Canonical Wnt signaling pathway; Adenomatous polyposis coil; Fibroblast-like synoviocytes
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Funding
- National Science Foundation of China [81273526, 81302783]
- Talent Project of Anhui Province [98]
- Research Project of Anhui Science and Technology University [ZRC2014473]
- Research Project of the Science and Technology Bureau of Chuzhou City [201306]
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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 p-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. (C) 2015 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.
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