系统性红斑狼疮异常 lncRNA-miRNA-mRNA 网络的构建与分析。

Reconstruction and analysis of the aberrant lncRNA-miRNA-mRNA network in systemic lupus erythematosus.

机构信息

Clinical Medical Research Centre, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, PR China.

Division of Nephrology, The First Affiliated Hospital, Jinan University, Guangzhou, PR China.

出版信息

Lupus. 2020 Apr;29(4):398-406. doi: 10.1177/0961203320908927. Epub 2020 Feb 18.

DOI:10.1177/0961203320908927

PMID:32070185

Abstract

OBJECTIVE

A new perspective of determining the pathophysiology of systemic lupus erythematosus (SLE) development is required. The current study explores the aberrant expression of long non-coding RNAs (lncRNA), microRNA (miRNA) and mRNA. The study further constructs and analyses the lncRNA-miRNA-mRNA network to elucidate their gene regulation roles in SLE.

METHOD

We extracted mRNA, lncRNA and miRNA from the whole venous blood of 20 SLE patients and 20 normal control (NC) healthy individuals. A lncRNA-mRNA-miRNA network in SLE was constructed using a bioinformatics approach. Subsequently, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed using the Cytoscape plug-in BinGo, the DAVID database and Cytoscape software to explore the function of mRNAs in this network.

RESULT

A total of 855 mRNA, 7311 lncRNA and 134 miRNA with differentially expressed profiles were identified. Meanwhile, we established a competing endogenous RNA (ceRNA) subnetwork composed of 52 differentially expressed lncRNAs (DElncRNAs), seven differentially expressed miRNAs and 10 differentially expressed mRNAs. We extracted the subnetwork from the ceRNA network and found that three novel miRNAs were key: hsa-miR-145, hsa-miR-17 and hsa-miR-143. We also deduced that the DElncRNAs MIAT and NEAT1 might play crucial roles in the pathogenesis of SLE. The results were verified by bioinformatics analysis.

CONCLUSION

Our results provide a novel perspective for studying lncRNA-related and miRNA-related ceRNA networks in SLE.

摘要

目的

需要确定系统性红斑狼疮（SLE）发病机制的新视角。本研究探讨了长非编码 RNA（lncRNA）、microRNA（miRNA）和信使 RNA（mRNA）的异常表达。本研究进一步构建和分析了 lncRNA-miRNA-mRNA 网络，以阐明它们在 SLE 中的基因调控作用。

方法

我们从 20 例 SLE 患者和 20 例正常对照（NC）健康个体的全静脉血中提取 mRNA、lncRNA 和 miRNA。使用生物信息学方法构建了 SLE 中的 lncRNA-miRNA-mRNA 网络。随后，使用 Cytoscape 插件 BinGo、DAVID 数据库和 Cytoscape 软件对基因本体论和京都基因与基因组百科全书通路分析进行了分析，以探讨该网络中 mRNAs 的功能。

结果

共鉴定出 855 条差异表达的 mRNA、7311 条 lncRNA 和 134 条差异表达的 miRNA。同时，我们建立了一个由 52 个差异表达的 lncRNA（DElncRNA）、7 个差异表达的 miRNA 和 10 个差异表达的 mRNA 组成的竞争内源性 RNA（ceRNA）子网络。我们从 ceRNA 网络中提取了该子网络，发现三个新的 miRNA 是关键：hsa-miR-145、hsa-miR-17 和 hsa-miR-143。我们还推断，DElncRNA MIAT 和 NEAT1 可能在 SLE 的发病机制中发挥关键作用。这些结果通过生物信息学分析得到了验证。