Differentially expressed mRNAs, lncRNAs, and miRNAs with associated co-expression and ceRNA networks in ankylosing spondylitis.

Differentially expressed mRNAs, lncRNAs, and miRNAs with associated co-expression and ceRNA networks in ankylosing spondylitis.
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强直性脊柱炎中差异表达的 mRNA、lncRNA 和 miRNA 以及相关的共表达和 ceRNA 网络

DOI:
10.18632/oncotarget.22708
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发表时间:
2017-12-26
期刊:
影响因子:
--
通讯作者:
Xu W
Xu W
中科院分区:
其他
文献类型:
--
作者:
Zhang C;Wang C;Jia Z;Tong W;Liu D;He C;Huang X;Xu W

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强直性脊柱炎(AS)是一种慢性自身免疫性疾病,以全身炎症和病理性成骨为特征。然而,AS 的遗传病因仍然很大程度上未知。本研究旨在探讨编码基因和非编码基因在AS遗传机制中的潜在作用。本研究利用微阵列分析,全面比较了 AS 患者和对照组髋关节韧带组织中的 lncRNA、microRNA 和 mRNA 谱。与对照组相比,AS 患者中共有 661 个 lncRNA、574 个 mRNA 和 22 个 microRNA 存在差异表达。然后使用实时聚合酶链反应验证了其中 22 个基因。进行基因本体和通路分析以探索差异表达基因的主要功能。这些途径主要涉及免疫调节、细胞间信号传导、成骨分化、蛋白质合成和降解。利用生物信息学方法构建基因信号转导网络、编码-非编码共表达网络和竞争性内源RNA表达网络。然后,鉴定出两种可以增加韧带成纤维细胞成骨分化潜力的 miRNA,miR-17-5p 和 miR-27b-3p。最后,使用定量实时聚合酶链式反应验证了差异表达的 5 个 lncRNA、4 个 miRNA 和 5 个 mRNA。这些结果表明 mRNA、lncRNA 和 microRNA 参与 AS 发病机制。这些发现可能有助于描述 AS 的发病机制,并为未来的 AS 患者提供新的治疗靶点。
Ankylosing spondylitis (AS) is a chronic autoimmune disease characterized by systemic inflammation and pathological osteogenesis. However, the genetic etiology of AS remains largely unknown. This study aimed to explore the potential role of coding and noncoding genes in the genetic mechanism of AS. Using microarray analyses, this study comprehensively compared lncRNA, microRNA, and mRNA profiles in hip joint ligament tissues from patients with AS and controls. A total of 661 lncRNAs, 574 mRNAs, and 22 microRNAs were differentially expressed in patients with AS compared with controls. Twenty-two of these genes were then validated using real-time polymerase chain reaction. Gene ontology and pathway analyses were performed to explore the principal functions of differentially expressed genes. The pathways were involved mainly in immune regulation, intercellular signaling, osteogenic differentiation, protein synthesis, and degradation. Gene signal transduction network, coding–noncoding co-expression network, and competing endogenous RNA expression network were constructed using bioinformatics methods. Then, two miRNAs, miR-17-5p and miR-27b-3p, that could increase the osteogenic differentiation potentials of ligament fibroblasts were identified. Finally, differentially expressed, five lncRNAs, four miRNAs, and five mRNAs were validated using quantitative real-time polymerase chain reaction. These results suggested that mRNAs, lncRNAs, and microRNAs were involved in AS pathogenesis. The findings might help characterize the pathogenesis of AS and provide novel therapeutic targets for patients with AS in the future.
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发表时间: 2014-08
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