Journal
SCIENTIFIC REPORTS
Volume 6, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/srep20059
Keywords
-
Categories
Funding
- Natural Science Fund of China [81373201, 31000406, 81273279, 81302560, 81260460, 81171735]
- National High Technology Research and Development Program of China [2012AA02A407]
Ask authors/readers for more resources
The main etiopathogenesis of rheumatoid arthritis (RA) is overexpressed inflammatory cytokines and tissue injury mediated by persistent NF-kappa B activation. MicroRNAs widely participate in the regulation of target gene expression and play important roles in various diseases. Here, we explored the mechanisms of microRNAs in RA. We found that microRNA (miR)-10a was downregulated in the fibroblast-like synoviocytes (FLSs) of RA patients compared with osteoarthritis (OA) controls, and this downregulation could be triggered by TNF-alpha and IL-1 beta in an NF-kappa B-dependent manner through promoting the expression of the YingYang 1 (YY1) transcription factor. Downregulated miR-10a could accelerate I kappa B degradation and NF-kappa B activation by targeting IRAK4, TAK1 and BTRC. This miR-10a-mediated NF-kappa B activation then significantly promoted the production of various inflammatory cytokines, including TNF-alpha, IL-1 beta, IL-6, IL-8, and MCP-1, and matrix metalloproteinase (MMP)-1 and MMP-13. In addition, transfection of a miR-10a inhibitor accelerated the proliferation and migration of FLSs. Collectively, our data demonstrates the existence of a novel NF-kappa B/YY1/miR-10a/NF-kappa B regulatory circuit that promotes the excessive secretion of NF-kappa B-mediated inflammatory cytokines and the proliferation and migration of RA FLSs. Thus, miR-10a acts as a switch to control this regulatory circuit and may serve as a diagnostic and therapeutic target for RA treatment.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available