顺铂诱导急性肾损伤关键基因的筛选和调控网络的构建

doi:10.3760/cma.j.issn.1007-1245.2022.13.015

摘要/Abstract

摘要： 目的　通过生物信息学鉴定顺铂诱导的急性肾损伤中的关键基因和通路，为急性肾损伤的治疗提供潜在靶点。方法　数据提取时间：建库至2021年3月1日。我们先从基因表达综合数据库（GEO）下载了GSE106993和GSE153625数据集，并使用R语言筛选出差异基因，再采用基因本体论（GO）富集分析和京都基因与基因组大百科全书数据库（KEGG）分析鉴定共同差异基因的主要功能，接着使用STRING数据库对共同的差异基因构建互作网络，并用Cytoscape筛选出关键基因。然后运用TransmiR v2.0数据库和miRWalk 2.0数据库构建转录因子（TF）/微小RNA（miRNA）/信使RNA（mRNA）调控网络。最后通过ETMC数据库筛选出靶向关键基因的中草药。结果　我们发现在顺铂诱导的急性肾损伤模型中上调基因有817个，下调基因有769个。肿瘤坏死因子信号通路、P53信号通路、代谢信号通路均是顺铂诱导的急性肾损伤的重要通路。通过蛋白互作网路，我们鉴定出8个关键基因（TrP53、EGF、Stat3、Jun、Casp3、Cdh1、Ptgs2、CAT）。并且构建了TF/miRNA/mRNA调控网络，TF 2个，miRNA 4个，mRNA 214个。ETMC数据库分析结果显示桑叶和半夏可用于顺铂诱导的急性肾损伤的治疗。结论　本研究通过生物信息学分析筛选出顺铂诱导的急性肾损伤中的8个关键基因和3个重要信号通路，为顺铂诱导急性肾损伤的治疗提供靶点。桑叶和半夏两味中药有望成为治疗急性肾损伤的中草药。

关键词: 顺铂, 急性肾损伤, 生物信息学, 中药

Abstract: Objective　To identify key signaling pathways and genes in cisplatin-induced acute kidney injury (CI-AKI) by bioinformatics, and to provide potential targets in treatment of AKI. Methods　The data were collected from the establishment to March 1,2021. The datasets of GSE106993 and GSE153625 were downloaded from Gene Expression Omnibus (GEO), and the differentially expressed genes (DEGs) were identified by R language. The gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to identify the main functions of the common differential genes. The STRING database was used to construct protein-protein interaction (PPI) networks, and the key genes were selected by Cytoscape. TransmiR v2.0 database and miRWalk2.0 database were used to construct transcription factor (TF)/microRNA (miRNA)/mRNA networks. Chinese herbal medicines targeting the key genes were screened by the ETMC database. Results　Eight hundred and seventeen up-regulated genes and 769 down-regulated genes were obtained from the CI-AKI models. Tumor necrosis factor (TNF) signaling pathway, P53 signaling pathway, and metabolic signaling pathway were important pathways in CI-AKI. Eight key genes, Trp53, EGF, Stat3, Jun, Casp3, Cdh1, Ptgs2, and CAT, were identified through PPI. We constructed TF/miRNA/mRNA regulatory networks, including 2 TFs, 4 miRNAs, and 214 mRNAs. The results of ETMC database analysis showed that Sangye and Banxia could be used in the treatment of CI-AKI. Conclusions　In this study, we identified 8 key genes and 3 important signaling pathways in the CI-AKI models by bioinformatics analysis, providing targets for the treatment of CI-AKI. And the two Chinese herbal medicines obtained from our research, Sangye and Banxia, are expected to be used in the treatment of CI-AKI.

Key words: Cisplatin, Acute kidney injury, Bioinformatic, Chinese medicine

杨玲云　徐锦雯　刘洵薇　成芸　周红霞　赵丽萍. 顺铂诱导急性肾损伤关键基因的筛选和调控网络的构建[J]. 国际医药卫生导报, 2022, 28(13): 1848-1853.

Yang Lingyun, Xu Jinwen, Liu Xunwei, Cheng Yun, Zhou Hongxia, Zhao Liping. Key gene screening and regulation network construction in cisplatin-induced acute kidney injury[J]. International Medicine and Health Guidance News, 2022, 28(13): 1848-1853.

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