LncRNA PICSAR promotes cell proliferation, migration and invasion of fibroblast-like synoviocytes by sponging miRNA-4701-5p in rheumatoid arthritis
LncRNA PICSAR promotes cell proliferation, migration and invasion of fibroblast-like synoviocytes by sponging miRNA-4701-5p in rheumatoid arthritis
复制标题
LncRNA PICSAR 通过海绵 miRNA-4701-5p 促进类风湿关节炎中成纤维细胞样滑膜细胞的细胞增殖、迁移和侵袭
DOI：
10.1016/j.ebiom.2019.11.024
复制
发表时间：
2019-12-01
期刊：
影响因子：
11.1
通讯作者：
Zheng, Song Guo
中科院分区：
文献类型：
--
作者：
Bi, Xuan;Guo, Xing Hua;Zheng, Song Guo
背景资料：长链非编码RNA（lncRNA）在类风湿性关节炎（RA）等多种自身免疫性疾病中发挥着重要作用，因此受到越来越多的关注。成纤维细胞样滑膜细胞（FLS）是增生性滑膜血管翳组织的重要组成部分，是RA滑膜增生和侵袭的主要效应细胞，可导致关节破坏。本研究旨在探讨lncRNA是否可以作为竞争性内源性RNA参与调节RA-FLS的病理行为。方法：采用lncRNA芯片技术，建立RA患者和健康对照（HC）FLS的lncRNA表达谱。通过定量实时PCR（qRT-PCR）对RA-FLS和滑液验证差异表达的lncRNA。在RA-FLS中评价lncRNA PICSAR下调的功能作用。我们进行了分子生物学分析，以预测具有PICSAR潜在结合位点的miRNA，并通过qRT-PCR进一步完善结果。采用荧光素酶报告基因分析法验证lncRNA PICSAR与miR-4701- 5 p的相互作用。采用Western Blot和qPCR鉴定目的基因和蛋白。结果：我们鉴定了一个长的基因间非蛋白编码RNA 162（LINC 00162），也称为lncRNA PICSAR（p38抑制皮肤鳞状细胞癌相关lincRNA），在RA-FLS和RA滑液中具有显著较高的表达。在lncRNA PICSAR抑制后，RA-FLS的细胞增殖、迁移、侵袭和促炎细胞因子的产生均发生显著变化。解释：我们的研究结果表明PICSAR可能在RA中通过海绵状吸收miR-4701 - 5 p促进滑膜侵袭和关节破坏中发挥重要作用，lncRNA PICSAR可能作为RA的生物标志物。(C)2019年，任作家。由爱思唯尔公司出版
Background: Long non-coding RNAs (lncRNAs) have drawn increasing attention because they play a pivotal role in various types of autoimmune diseases, including rheumatoid arthritis (RA). Fibroblast-like synoviocytes (FLSs), a prominent component of hyperplastic synovial pannus tissue, are the primary effector cells in RA synovial hyperplasia and invasion which can lead to joint destruction. In this study, we investigated whether lncRNAs could act as competing endogenous RNAs to regulate the pathological behaviors of RA-FLSs.Methods: LncRNA microarray was conducted to establish lncRNA expression profiles in FLSs isolated from RA patients and healthy controls (HCs). Differentially expressed lncRNAs were verified by quantitative real-time PCR (qRT-PCR) on RA-FLSs and synovial fluid. The functional role of lncRNA PICSAR downregulation was evaluated in RA-FLSs. We conducted molecular biological analysis to predict miRNAs which have a potential binding site for PICSAR and further refined the results by qRT-PCR. Luciferase reporter assay was adopted to validate the interaction of lncRNA PICSAR and miR-4701-5p. Western Blot and qPCR were used to identify the target gene and protein. The functional role of miR-4701-5p upregulation was examined in RA-FLSs.Findings: We identified a long intergenic non-protein-coding RNA162 (LINC00162), also known as lncRNA PICSAR (p38 inhibited cutaneous squamous cell carcinoma associated lincRNA), has significantly higher expression in RA-FLSs and RA synovial fluid. The cell proliferation, migration, invasion and proinflammatory cytokines production of RA-FLSs showed significant alterations after the lncRNA PICSAR suppression. Mechanistically, lncRNA PICSAR functioned through sponging miR-4701-5p in RA-FLSs.Interpretation: Our results reveal PICSAR may exert an essential role in promoting synovial invasion and joint destruction by sponging miR-4701-5p in RA and that lncRNA PICSAR may act as a biomarker of RA. (C) 2019 The Authors. Published by Elsevier B.V.