Increased long noncoding RNA LINK-A contributes to rheumatoid synovial inflammation and aggression
Jingnan Wang, … , Liuqin Liang, Hanshi Xu
Jingnan Wang, … , Liuqin Liang, Hanshi Xu
Published December 8, 2021
Citation Information: JCI Insight. 2021;6(23):e146757. https://doi.org/10.1172/jci.insight.146757.
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Research Article Immunology

Increased long noncoding RNA LINK-A contributes to rheumatoid synovial inflammation and aggression

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

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Figure 7

The relationship between miR-1262 and HIF-1α in RA FLSs.

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The relationship between miR-1262 and HIF-1α in RA FLSs. RA FLSs were tr...
RA FLSs were treated with miRNA inhibitors or mimics or transfected with HIF-1α siRNA (si-HIF-1α-1 or si-HIF-1α-3). The miRNAs and mRNA were detected using RT-qPCR. The protein levels were measured by Western blot. (A) Effect of HIF-1α knockdown on the expression of miR-1262. (B and C) Effect of miR-1262 inhibitor (B) or mimics (C) on mRNA expression of HIF-1α. (D) Effect of miR-1262 inhibitor or mimics on protein expression of total HIF-1α. (E) Effect of miR-1262 inhibitor or mimics on protein expression of nuclear HIF-1α. Data (A–C) are presented as the mean ± SD from at least 3 independent experiments. Graphs (D and E, right panel) are expressed as the mean ± SD of densitometry quantification of Western blot results from at least 3 independent experiments. (F) Proposed model for LINK-A–mediated regulation of the synovial migration, invasion, and inflammation in RA FLSs.