Long noncoding RNA LERFS negatively regulates rheumatoid synovial aggression and proliferation
Long noncoding RNA LERFS negatively regulates rheumatoid synovial aggression and proliferation
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长非编码RNA LERFS负调节类风湿滑膜侵袭和增殖
DOI：
10.1172/jci97965
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发表时间：
2018-10-01
影响因子：
15.9
通讯作者：
Xu, Hanshi
中科院分区：
文献类型：
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作者：
Zou, Yaoyao;Xu, Siqi;Xu, Hanshi
成纤维细胞样滑膜细胞（FLS）是类风湿关节炎（RA）滑膜侵袭和关节破坏的关键。长链非编码RNA（lncRNA）在RA中的作用在很大程度上是未知的。在这里，我们确定了一个lncRNA，LERFS（低表达类风湿性成纤维细胞样滑膜细胞），负调控迁移，入侵，并通过与异质性核核糖核蛋白Q（hnRNP Q）的相互作用FLS增殖。在健康条件下，通过与RhoA、Rac 1和CDC 42的mRNA结合，LERFS-hnRNP Q复合物降低了靶mRNA的稳定性或翻译，并下调了它们的蛋白水平。但在RA FLS中，LERFS水平的降低诱导LERFS-hnRNP Q复合物的减少，这减少了hnRNP Q与靶mRNA的结合，从而增加了靶mRNA的稳定性或翻译。这些发现表明，滑膜LERFS的减少可能有助于RA的滑膜攻击和关节破坏，靶向lncRNA LERFS可能对RA患者具有治疗潜力。
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 (lowly 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.