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

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-...

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Autores principales: Wang, Jingnan, Shen, Chuyu, Li, Ruiru, Wang, Cuicui, Xiao, Youjun, Kuang, Yu, Lao, Minxi, Xu, Siqi, Shi, Maohua, Cai, Xiaoyan, Liang, Liuqin, Xu, Hanshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Clinical Investigation 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8675191/
https://www.ncbi.nlm.nih.gov/pubmed/34877935
http://dx.doi.org/10.1172/jci.insight.146757
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author Wang, Jingnan
Shen, Chuyu
Li, Ruiru
Wang, Cuicui
Xiao, Youjun
Kuang, Yu
Lao, Minxi
Xu, Siqi
Shi, Maohua
Cai, Xiaoyan
Liang, Liuqin
Xu, Hanshi
author_facet Wang, Jingnan
Shen, Chuyu
Li, Ruiru
Wang, Cuicui
Xiao, Youjun
Kuang, Yu
Lao, Minxi
Xu, Siqi
Shi, Maohua
Cai, Xiaoyan
Liang, Liuqin
Xu, Hanshi
author_sort Wang, Jingnan
collection PubMed
description 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.
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spelling pubmed-86751912021-12-21 Increased long noncoding RNA LINK-A contributes to rheumatoid synovial inflammation and aggression Wang, Jingnan Shen, Chuyu Li, Ruiru Wang, Cuicui Xiao, Youjun Kuang, Yu Lao, Minxi Xu, Siqi Shi, Maohua Cai, Xiaoyan Liang, Liuqin Xu, Hanshi JCI Insight Research Article 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. American Society for Clinical Investigation 2021-12-08 /pmc/articles/PMC8675191/ /pubmed/34877935 http://dx.doi.org/10.1172/jci.insight.146757 Text en © 2021 Wang et al. https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Wang, Jingnan
Shen, Chuyu
Li, Ruiru
Wang, Cuicui
Xiao, Youjun
Kuang, Yu
Lao, Minxi
Xu, Siqi
Shi, Maohua
Cai, Xiaoyan
Liang, Liuqin
Xu, Hanshi
Increased long noncoding RNA LINK-A contributes to rheumatoid synovial inflammation and aggression
title Increased long noncoding RNA LINK-A contributes to rheumatoid synovial inflammation and aggression
title_full Increased long noncoding RNA LINK-A contributes to rheumatoid synovial inflammation and aggression
title_fullStr Increased long noncoding RNA LINK-A contributes to rheumatoid synovial inflammation and aggression
title_full_unstemmed Increased long noncoding RNA LINK-A contributes to rheumatoid synovial inflammation and aggression
title_short Increased long noncoding RNA LINK-A contributes to rheumatoid synovial inflammation and aggression
title_sort increased long noncoding rna link-a contributes to rheumatoid synovial inflammation and aggression
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8675191/
https://www.ncbi.nlm.nih.gov/pubmed/34877935
http://dx.doi.org/10.1172/jci.insight.146757
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