Abstract
Fibroblast-like synoviocytes (FLSs) play a key role in controlling synovial inflammation and joint destruction in rheumatoid arthritis (RA). The contribution of long noncoding RNAs (lncRNAs) to RA is largely unknown. Here, we show that the lncRNA LINK-A, located mainly in cytoplasm, has higher-than-normal expression in synovial tissues and FLSs from patients with RA. Synovial LINK-A expression was positively correlated with the severity of synovitis in patients with RA. LINK-A knockdown decreased migration, invasion, and expression and secretion of matrix metalloproteinases and proinflammatory cytokines in RA FLSs. Mechanistically, LINK-A controlled RA FLS inflammation and invasion through regulation of tyrosine protein kinase 6–mediated and leucine-rich repeat kinase 2–mediated HIF-1α. On the other hand, we also demonstrate that LINK-A could bind with microRNA 1262 as a sponge to control RA FLS aggression but not inflammation. Our findings suggest that increased level of LINK-A may contribute to FLS-mediated rheumatoid synovial inflammation and aggression. LINK-A might be a potential therapeutic target for RA.
Authors
Jingnan Wang, Chuyu Shen, Ruiru Li, Cuicui Wang, Youjun Xiao, Yu Kuang, Minxi Lao, Siqi Xu, Maohua Shi, Xiaoyan Cai, Liuqin Liang, Hanshi Xu
This file is in Adobe Acrobat (PDF) format. If you have not installed and configured the Adobe Acrobat Reader on your system.
Having trouble reading a PDF?
PDFs are designed to be printed out and read, but if you prefer to read them online, you may find it easier if you increase the view size to 125%.
Having trouble saving a PDF?
Many versions of the free Acrobat Reader do not allow Save. You must instead save the PDF from the JCI Online page you downloaded it from. PC users: Right-click on the Download link and choose the option that says something like "Save Link As...". Mac users should hold the mouse button down on the link to get these same options.
Having trouble printing a PDF?
- Try printing one page at a time or to a newer printer.
- Try saving the file to disk before printing rather than opening it "on the fly." This requires that you configure your browser to "Save" rather than "Launch Application" for the file type "application/pdf", and can usually be done in the "Helper Applications" options.
- Make sure you are using the latest version of Adobe's Acrobat Reader.
