Long noncoding RNA LERFS negatively regulates rheumatoid synovial aggression and proliferation
Fibroblast-like synoviocytes (FLSs) are critical to synovial aggression and joint destruction in rheumatoid arthritis (RA). The role of long noncoding RNAs (lncRNAs) in RA is largely unknown. Here, we identified a lncRNA, LERFS (jowly expressed in rheumatoid fibroblast-like synoviocytes), that negat...
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Published in | The Journal of clinical investigation Vol. 128; no. 10; pp. 4510 - 4524 |
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Main Authors | , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Ann Arbor
American Society for Clinical Investigation
01.10.2018
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Subjects | |
Online Access | Get full text |
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Summary: | Fibroblast-like synoviocytes (FLSs) are critical to synovial aggression and joint destruction in rheumatoid arthritis (RA). The role of long noncoding RNAs (lncRNAs) in RA is largely unknown. Here, we identified a lncRNA, LERFS (jowly expressed in rheumatoid fibroblast-like synoviocytes), that negatively regulates the migration, invasion, and proliferation of FLSs through interaction with heterogeneous nuclear ribonucleoprotein Q (hnRNP Q). Under healthy conditions, by binding to the mRNA of RhoA, Rac1, and CDC42 - the small GTPase proteins that control the motility and proliferation of FLSs - the LERFS-hnRNP Q complex decreased the stability or translation of target mRNAs and downregulated their protein levels. But in RA FLSs, decreased LERFS levels induced a reduction of the LERFS-hnRNP Q complex, which reduced the binding of hnRNP Q to target mRNA and therefore increased the stability or translation of target mRNA. These findings suggest that a decrease in synovial LERFS may contribute to synovial aggression and joint destruction in RA and that targeting the lncRNA LERFS may have therapeutic potential in patients with RA. |
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ISSN: | 0021-9738 1558-8238 |
DOI: | 10.1172/JCI97965. |