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运用生物信息学方法鉴定糖尿病肾病治疗干预的生物学靶点

Identification of biological targets of therapeutic intervention for diabetic nephropathy with bioinformatics approach.

作者信息

Wu T, Li Q, Wu T, Liu H Y

机构信息

Department of Nephrology, The Second Hospital of Shandong University, Jinan, Shandong Province, China.

Institute of Biomedical Engineering, School of Medicine, Shandong University, Jinan, Shandong Province, China.

出版信息

Exp Clin Endocrinol Diabetes. 2014 Nov;122(10):587-91. doi: 10.1055/s-0034-1382033. Epub 2014 Jul 8.

Abstract

We aimed to discover the potential microRNA (miRNA) targets for diabetic nephropathy (DN) treatment. The microarray data of GSE1009 was downloaded from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) between DN patients and normal individuals were analyzed using limma package. The significant miRNAs targeting DEGs were collected based on Web-based Gene Set Enrichment Analysis Toolkit (WebGestalt) system. Then we predicted the protein-protein interaction (PPI) pairs regulated by significant miRNAs and constructed the PPI pairs-miRNA network using Cytoscape software. Besides, the significant function modules were explored using Molecular Complex Detection (MCODE) and Biological Networks Gene Ontology (BiNGO) plugin. Total 752 DEGs were obtained, including 318 down-regulated ones and 434 up-regulated ones. There were 10 significant miRNAs, among which miRNA-25 was the most significant. The PPI pairs-miRNA network was established with 103 PPI pairs and 10 miRNAs. Three function modules were obtained, including module A involved with miRNA-29, module B with miRNA-106 and module C with miRNA-124A and miRNA-21B. MiRNA-25, 29, 124 and 21 play key roles in DN progression and these miRNAs may be potential targets for DN treatment.

摘要

我们旨在发现糖尿病肾病(DN)治疗的潜在微小RNA(miRNA)靶点。从基因表达综合数据库(GEO)下载了GSE1009的微阵列数据。使用limma软件包分析DN患者和正常个体之间的差异表达基因(DEG)。基于基于网络的基因集富集分析工具包(WebGestalt)系统收集靶向DEG的显著miRNA。然后我们预测了由显著miRNA调控的蛋白质-蛋白质相互作用(PPI)对,并使用Cytoscape软件构建了PPI对-miRNA网络。此外,使用分子复合物检测(MCODE)和生物网络基因本体(BiNGO)插件探索显著功能模块。共获得752个DEG,包括318个下调的和434个上调的。有10个显著的miRNA,其中miRNA-25最为显著。建立了包含103个PPI对和10个miRNA的PPI对-miRNA网络。获得了三个功能模块,包括与miRNA-29相关的模块A、与miRNA-106相关的模块B以及与miRNA-124A和miRNA-21B相关的模块C。miRNA-25、29、124和21在DN进展中起关键作用,这些miRNA可能是DN治疗的潜在靶点。

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