关键词: bioinformatics analysis competing endogenous RNAs differentially expressed genes enrichment analysis systemic lupus erythematosus

来  源:   DOI:10.3389/fmed.2024.1383186   PDF(Pubmed)

Abstract:
UNASSIGNED: Systemic lupus erythematosus (SLE) is a disease characterised by immune inflammation and damage to multiple organs. Recent investigations have linked competing endogenous RNAs (ceRNAs) to lupus. However, the exact mechanism through which the ceRNAs network affects SLE is still unclear. This study aims to investigate the regulatory functions of the ceRNAs network, which are important pathways that control the pathophysiological processes of SLE.
UNASSIGNED: CircRNA microarray for our tested assays were derived from bone marrow samples from three healthy individuals and three SLE patients in our hospital. The other sequencing data of circRNA, miRNA and mRNA were obtained from Gene Expression Omnibus (GEO) datasets. Using the limma package of R program, the differential expression of mRNA and miRNA in the GEO database was discovered. Then predicted miRNA-mRNA and circRNA-miRNA were established using miRMap, miRanda, miRDB, TargetScan, and miTarBase. CircRNA-miRNA-mRNA ceRNA network was constructed using Cytoscape, and hub genes were screened using a protein-protein interaction network. Immune infiltration analysis of the hub gene was also performed by CIBERSORT and GSEA.
UNASSIGNED: 230 overlapped circRNAs, 86 DEmiRNAs and 2083 DEmRNAs were identified in SLE patients as compared to healthy controls. We constructed a circRNA-miRNA-mRNA ceRNAs network contained 11 overlapped circRNAs, 9 miRNAs and 51 mRNAs. ESR1 and SIRT1 were the most frequently associated protein-protein interactions in the PPI network. KEGG analysis showed that DEGs was enriched in FoxO signaling pathway as well as lipids and atherosclerosis. We constructed a novel circRNA-miRNA-mRNA ceRNA network (HSA circ 0000345- HSA miR-22-3-P-ESR1/SIRT1) that may have a major impact on SLE.
UNASSIGNED: Through this bioinformatics and integrated analysis, we suggest a regulatory role for ceRNA network in the pathogenesis and treatment of SLE.
摘要:
系统性红斑狼疮(SLE)是一种以免疫炎症和多器官损伤为特征的疾病。最近的研究已经将竞争性内源性RNA(ceRNA)与狼疮联系起来。然而,ceRNAs网络影响SLE的确切机制尚不清楚。本研究旨在探讨ceRNAs网络的调控功能,是控制SLE病理生理过程的重要途径。
用于我们测试的测定的CircRNA微阵列来自我们医院的三个健康个体和三个SLE患者的骨髓样本。circRNA的其他测序数据,miRNA和mRNA从基因表达综合(GEO)数据集获得。使用R程序的limma包,在GEO数据库中发现mRNA和miRNA的差异表达。然后使用miRMap建立预测的miRNA-mRNA和circRNA-miRNA,miRanda,miRDB,TargetScan,还有mitarBase.使用CytoscRNA构建CircRNA-miRNA-mRNAceRNA网络,和hub基因使用蛋白质-蛋白质相互作用网络进行筛选。中枢基因的免疫浸润分析也由CIBERSORT和GSEA进行。
230个重叠的circRNAs,与健康对照相比,在SLE患者中鉴定了86个DEmiRNA和2083个DEmRNA。我们构建了一个circRNA-miRNA-mRNAceRNAs网络,包含11个重叠的circRNAs,9个miRNA和51个mRNA。ESR1和SIRT1是PPI网络中最常见的相关蛋白质-蛋白质相互作用。KEGG分析显示,DEGs在FoxO信号通路以及脂质和动脉粥样硬化中富集。我们构建了一个新的circRNA-miRNA-mRNAceRNA网络(HSAcirc0000345-HSAmiR-22-3-P-ESR1/SIRT1),可能对SLE产生重大影响。
通过这种生物信息学和综合分析,我们建议ceRNA网络在SLE的发病机制和治疗中的调节作用。
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