Long Non-Coding RNA GAPLINC Promotes Tumor-Like Biologic Behaviors of Fibroblast-Like Synoviocytes as MicroRNA Sponging in Rheumatoid Arthritis Patients.
Long Non-Coding RNA GAPLINC Promotes Tumor-Like Biologic Behaviors of Fibroblast-Like Synoviocytes as MicroRNA Sponging in Rheumatoid Arthritis Patients.
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长非编码 RNA GAPLINC 作为 MicroRNA 海绵促进类风湿关节炎患者成纤维细胞样滑膜细胞的肿瘤样生物学行为
DOI：
10.3389/fimmu.2018.00702
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发表时间：
2018
影响因子：
7.3
通讯作者：
Zheng SG
中科院分区：
文献类型：
--
作者：
Mo BY;Guo XH;Yang MR;Liu F;Bi X;Liu Y;Fang LK;Luo XQ;Wang J;Bellanti JA;Pan YF;Zheng SG
快速积累的证据表明，长链非编码RNA （long non-coding RNA, LncRNAs）是一类具有多种功能和机制的非编码转录RNA分子，在许多人类炎症性疾病的发病机制中发挥着重要作用。尽管一些lncrna在类风湿关节炎（RA）患者的血浆、T细胞和滑膜组织中过表达，但对于这些转录本在这些患者的成纤维细胞样滑膜细胞（FLSs）中所起的作用尚缺乏了解。在这里，我们的研究表明，GAPLINC，一种在肿瘤学中新发现的功能性LncRNA，在RA的FLSs中比在创伤性损伤患者中表达程度更高。在RA-FLS细胞中抑制GAPLINC显示出细胞增殖、侵袭、迁移和促炎细胞因子产生的显著改变。此外，我们对GAPLINC基因序列进行了初步的生物信息学分析，以寻找其靶分子，使用miRanda， PITA， RNAhybrid算法，京都基因和基因组百科全书，以及基因本体分析。由于结果预测了一些microrna和mRNA可能与GAPLINC相互作用，我们基于竞争内源RNA理论模拟了一个基因协同作用网络模型。对该模型的进一步验证表明，沉默GAPLINC可增加miR-382-5p和miR-575的表达。本研究结果提示，GAPLINC可能作为一种新型的microrna海绵剂，影响RA-FLSs的生物学特性。此外，GAPLINC还可能以mir -382-5p依赖和mir -575依赖的方式促进RA-FLS肿瘤样行为。基于这些发现，LncRNA GAPLINC可能为RA患者提供一个新的有价值的治疗靶点。
Rapidly accumulating evidence has now suggested that the long non-coding RNAs (LncRNAs), a large and diverse class of non-coding transcribed RNA molecules with diverse functional roles and mechanisms, play a major role in the pathogenesis of many human inflammatory diseases. Although some LncRNAs are overexpressed in plasma, T cell, and synovial tissues of patients with rheumatoid arthritis (RA), there is a dearth of knowledge in what role these transcripts play in fibroblast-like synoviocytes (FLSs) of these patients. Here, our studies showed that GAPLINC, a newly identified functional LncRNA in oncology, displayed a greater degree of expression in FLSs from RA than in patients with traumatic injury. GAPLINC suppression in RA-FLS cells revealed significant alterations in cell proliferation, invasion, migration, and proinflammatory cytokines production. Additionally, we performed a preliminary bioinformatics analysis of GAPLINC gene sequence in order to find its target molecules, using miRanda, PITA, RNAhybrid algorithms, Kyoto encyclopedia of genes and genomes, and gene ontology analysis. Since the results predicted that some of microRNAs and mRNA may interact with GAPLINC, we simulated a gene co-action network model based on a competitive endogenous RNA theory. Further verification of this model demonstrated that silencing of GAPLINC increased miR-382-5p and miR-575 expression. The results of this study suggest that GAPLINC may function as a novel microRNAs sponging agent affecting the biological characteristics of RA-FLSs. Additionally, GAPLINC may also promote RA-FLS tumor-like behaviors in a miR-382-5p-dependent and miR-575-dependent manner. Based upon these findings, LncRNA GAPLINC may provide a novel valuable therapeutic target for RA patients.
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