MicroRNA-663 activates the canonical Wnt signaling through the adenomatous polyposis coli suppression

• MiR-663 is specifically up-regulated in RA patients compared with controls.
• Increased miR-663 results in a marked reduction of APC expression.
• MiR-663 indirectly affects the Wnt signaling by targeting APC.
• MiR-663 displays an important role in the pathogenesis of RA.

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 β-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.