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Integrated analysis of competing endogenous RNA networks in peripheral blood mononuclear cells of systemic lupus erythematosus
Journal of Translational Medicine ( IF 6.1 ) Pub Date : 2021-08-21 , DOI: 10.1186/s12967-021-03033-8
Wencong Song 1, 2 , Jie Qiu 3 , Lianghong Yin 2 , Xiaoping Hong 1 , Weier Dai 4 , Donge Tang 1, 5 , Dongzhou Liu 1 , Yong Dai 1, 5
Affiliation  

Systemic lupus erythematosus (SLE) is an autoimmune disease with a complicated pathogenesis, and its aetiology has not been clearly unveiled. The lack of effective diagnosis and treatment methods makes it necessary to explore the molecular mechanism of SLE. We aimed to identify some critical signalling pathways and key competing endogenous RNAs (ceRNAs) underlying the molecular mechanism of SLE and to map out the systematic signalling networks by integrating the data on different kinds of RNAs. Peripheral blood mononuclear cells (PBMCs) were collected from both SLE patients and healthy subjects, RNA was extracted from the PBMCs, and RNA libraries including ribosomal RNA-depleted strand-specific libraries and small RNA libraries were built for deep RNA sequencing (RNA-seq). RNA-seq yielded differential expression profiles of lncRNAs/circRNAs/miRNAs/mRNAs related to SLE. The DAVID database (v. 6.8) was employed for Gene Ontology (GO) and KEGG pathway analysis. ceRNA networks (circRNA/lncRNA-miRNA-mRNA) were constructed and visualized using Cytoscape software (v. 3.5.0). The TargetScan and miRanda databases were used to predict target relationships in ceRNA networks. qRT-PCR was used to verify our data. Differential expression of ceRNAs related to SLE was detected in SLE patients’ PBMCs: 644 mRNAs (384 upregulated, 260 downregulated), 326 miRNAs (223 upregulated, 103 downregulated), 221 lncRNAs (79 upregulated, 142 downregulated), and 31 circRNAs (21 upregulated, 10 downregulated). We drew ceRNA signalling networks made up of the differentially expressed mRNAs/miRNAs/lncRNAs/circRNAs mentioned above, and the hub genes included IRF5, IFNAR2, TLR7, IRAK4, STAT1, STAT2, C2, and Tyk2. These hub genes were involved in ceRNA signalling pathways, such as the IL-17 signalling pathway and type I interferon signalling pathway. We explored the differential expression profiles of various kinds of ceRNAs and integrated signalling networks constructed by ceRNAs. Our findings offer new insights into the pathogenesis of SLE and hint at therapeutic strategies.

中文翻译:

系统性红斑狼疮外周血单个核细胞竞争性内源RNA网络的综合分析

系统性红斑狼疮(SLE)是一种发病机制复杂的自身免疫性疾病,其病因尚未明确。由于缺乏有效的诊断和治疗方法,有必要探讨SLE的分子机制。我们的目的是确定 SLE 分子机制背后的一些关键信号通路和关键竞争性内源性 RNA (ceRNA),并通过整合不同种类 RNA 的数据来绘制系统信号网络。从SLE患者和健康受试者中收集外周血单核细胞(PBMC),从PBMC中提取RNA,并构建RNA文库,包括核糖体RNA耗尽链特异性文库和小RNA文库,用于深度RNA测序(RNA-seq) )。RNA-seq 产生了与 SLE 相关的 lncRNA/circRNA/miRNA/mRNA 的差异表达谱。DAVID 数据库(v. 6.8)用于基因本体(GO)和 KEGG 通路分析。使用 Cytoscape 软件(v. 3.5.0)构建和可视化 ceRNA 网络(circRNA/lncRNA-miRNA-mRNA)。TargetScan 和 miRanda 数据库用于预测 ceRNA 网络中的目标关系。qRT-PCR 用于验证我们的数据。在SLE患者的PBMC中检测到与SLE相关的ceRNA的差异表达:644个mRNA(384个上调,260个下调),326个miRNA(223个上调,103个下调),221个lncRNA(79个上调,142个下调)和31个circRNA(21个)上调,10 下调)。我们绘制了由上述差异表达的mRNA/miRNA/lncRNA/circRNA组成的ceRNA信号网络,枢纽基因包括IRF5、IFNAR2、TLR7、IRAK4、STAT1、STAT2、C2和Tyk2。这些hub基因参与ceRNA信号通路,例如IL-17信号通路和I型干扰素信号通路。我们探索了各种ceRNA的差异表达谱以及由ceRNA构建的整合信号网络。我们的研究结果为系统性红斑狼疮的发病机制提供了新的见解,并暗示了治疗策略。
更新日期:2021-08-23
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