Long Noncoding RNA HAFML Promotes Migration and Invasion of Rheumatoid Fibroblast-like Synoviocytes.
Long Noncoding RNA HAFML Promotes Migration and Invasion of Rheumatoid Fibroblast-like Synoviocytes.
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DOI：
10.4049/jimmunol.2200453
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发表时间：
2022-11
影响因子：
4.4
通讯作者：
Siqi Xu;Di Liu;Y. Kuang;Ruiru Li;Jingnan Wang;M. Shi;Y. Zou;Q. Qiu;L. Liang;Youjun Xiao-Youjun-X
中科院分区：
文献类型：
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作者：
Siqi Xu;Di Liu;Y. Kuang;Ruiru Li;Jingnan Wang;M. Shi;Y. Zou;Q. Qiu;L. Liang;Youjun Xiao-Youjun-X
成纤维细胞样滑膜细胞（FLS）表现出的侵袭性表型对类风湿性关节炎（RA）关节破坏的进展至关重要。长链非编码RNA（lncRNA）在多种疾病的发病机制中起着至关重要的作用;然而，很少有人被确定能够控制RA的关节损伤。在这项研究中，我们鉴定了一种lncRNA，ENST 00000509194，它在RA患者的FLS和滑膜组织中以异常高的水平表达。ENST 00000509194通过与人Ag R（HuR，也称为ELAVL 1）（一种主要稳定mRNA的RNA结合蛋白）相互作用积极调节FLS的迁移和侵袭。ENST 00000509194直接与细胞质中的HuR结合形成复合物，该复合物通过稳定APPL 2 mRNA来促进内吞衔接蛋白APPL 2的表达。HuR或APPL 2的敲低损害了RA FLS的迁移和侵袭。鉴于其与HuR和FLS迁移的密切关联，我们将ENST 00000509194命名为HAFML（HuR相关成纤维细胞迁移lncRNA）。我们的研究结果表明，滑膜HAFML的增加可能有助于FLS介导的类风湿性滑膜侵略和关节破坏，lncRNA HAFML可能是一个潜在的治疗目标失调的成纤维细胞在广泛的疾病。
The aggressive phenotype exhibited by fibroblast-like synoviocytes (FLSs) is critical for the progression of joint destruction in rheumatoid arthritis (RA). Long noncoding RNAs (lncRNAs) have crucial roles in the pathogenesis of diverse disorders; however, few have been identified that might be able to control the joint damage in RA. In this study, we identified an lncRNA, ENST00000509194, which was expressed at abnormally high levels in FLSs and synovial tissues from patients with RA. ENST00000509194 positively modulates the migration and invasion of FLSs by interacting with human Ag R (HuR, also called ELAVL1), an RNA-binding protein that mainly stabilizes mRNAs. ENST00000509194 binds directly to HuR in the cytoplasm to form a complex that promotes the expression of the endocytic adaptor protein APPL2 by stabilizing APPL2 mRNA. Knockdown of HuR or APPL2 impaired the migration and invasion of RA FLSs. Given its close association with HuR and FLS migration, we named ENST00000509194 as HAFML (HuR-associated fibroblast migratory lncRNA). Our findings suggest that an increase in synovial HAFML might contribute to FLS-mediated rheumatoid synovial aggression and joint destruction, and that the lncRNA HAFML might be a potential therapeutic target for dysregulated fibroblasts in a wide range of diseases.