Identification of Key circRNAs/lncRNAs/miRNAs/mRNAs and Pathways in Preeclampsia Using Bioinformatics Analysis
Identification of Key circRNAs/lncRNAs/miRNAs/mRNAs and Pathways in Preeclampsia Using Bioinformatics Analysis
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DOI：
10.12659/msm.912801
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发表时间：
2019-03-05
影响因子：
3.1
通讯作者：
Xie, Lan
中科院分区：
文献类型：
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作者：
Liu, Siwei;Xie, Xie;Xie, Lan
背景资料：材料/方法：利用RNA-seq技术和GEO数据库，获得与子痫前期（preeclampsia，PE）相关的circRNAs/lncRNAs/miRNAs/mRNAs的表达谱。差异表达的RNA使用R.使用GSEA软件（v.3.0）进行基因集富集分析（GSEA），并使用R.利用大卫数据库（v.6.8）分析基因的功能分类、基因间的关联以及相应的基因本体（GO）分类。使用R可视化软件包GOPlot来更好地可视化基因与所选功能类别之间的关系。使用Cytoscape软件（v.3.6.0）构建可视化circRNA/lncRNA-miRNA-mRNA之间的相关性的CeRNA网络。利用Targetscan和米兰达数据库预测circRNA/lncRNA-miRNA-mRNA之间的靶标关系。结果：与正常胎盘组织相比，胎盘组织中的jak-stat信号通路被激活，miR-100 - 5 p表达下调。结论：miR-100 - 5 p可能抑制PE的发生，LIF、LINC 01492和hsa_circ_0088196可能通过抑制miR-100 - 5 p而促进PE的发生。jak-stat信号通路被激活并参与PE进展。
Background: This study aimed to identify significantly altered circRNAs/lncRNAs/miRNAs/mRNAs pathways in preeclampsia (PE), investigate their target relationships, and determine their biological functions.Material/Methods: Base on RNA-seq technique and the GEO database, expression profiles of circRNAs/lncRNAs/miRNAs/mRNAs related to PE were obtained. Differentially expressed RNAs were determined using the Limma package in R. Gene set enrichment analysis (GSEA) was performed using GSEA software (v. 3.0) and illustrated by ClusterProfiler and ggplot2 package in R. DAVID database (v. 6.8) was implemented to analyze functional categories and the association between genes and the corresponding Gene Ontology (GO) classification. The R visualization package GOPlot was used to get a better visualization of the relationships between genes and the selected functional categories. CeRNA networks which visualized the correlations between circRNA/lncRNA-miRNA-mRNA were constructed using Cytoscape software (v. 3.6.0). Targetscan and miRanda database were used to predict target relationships between circRNA/lncRNA-miRNA-mRNA. QRT-PCR and luciferase reporter assay were used to verify the expression and target relationship of has_circ_0088196/LINC01492/miR-100-5p/LIF (leukemia inhibitory factor).Results: The jak-stat signaling pathway was activated and miR-100-5p was downregulated in PE compared with normal tissues both in collected placental tissue samples and GEO database. Upregulated LIF, LINC01492, and hsa_circ_0088196 were negatively correlated with miR-100-5p expression and had a targeted relationship with miR-100-5p.Conclusions: miR-100-5p may suppress PE development, while LIF, LINC01492, and hsa_circ_0088196 may promote it though inhibiting miR-100-5p. The jak-stat signaling pathway was activated and involved in PE progression.