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缺血性和特发性心肌病中的铁死亡相关基因:潜在药理学靶点的筛选

Ferroptosis Related Genes in Ischemic and Idiopathic Cardiomyopathy: Screening for Potential Pharmacological Targets.

作者信息

Jiang Yufeng, Chen Ling, Chao Zhujun, Chen Tan, Zhou Yafeng

机构信息

Department of Cardiology, Suzhou Dushu Lake Hospital, Dushu Lake Hospital Affiliated to Soochow University, Medical Center of Soochow University, Suzhou, China.

Department of Endocrinology, The First Affiliated Hospital of Soochow University, Suzhou, China.

出版信息

Front Cell Dev Biol. 2022 Mar 3;10:817819. doi: 10.3389/fcell.2022.817819. eCollection 2022.

Abstract

Ferroptosis is a new form of cell death recently discovered that is distinct from apoptosis, necrosis and autophagy. This article is expected to provide a new direction for the treatment of cardiomyopathy in the future by screening potential drug targets associated with ferroptosis. Differential expression analysis of GSE5406 from the Gene Expression Omnibus (GEO) database was performed using the GEO2R tool. Functional annotation of ferroptosis related genes was also performed. Then we constructed protein-protein interaction networks and identified hub genes using Cytoscape. The candidates for pharmacological compounds targeting the hub genes were screened by cMap. Totally 15 ferroptosis related genes (4 upregulated and 11 downregulated) for ischemic cardiomyopathy and 17 ferroptosis related genes (13 upregulated and 4 downregulated) for idiopathic cardiomyopathy were found. The biological processes involved in these genes mainly include negative regulation of apoptotic process, flavonoid metabolic process, response to drug for ischemic cardiomyopathy and cellular response to fibroblast growth factor stimulus, negative regulation of apoptotic process, and response to drug for idiopathic cardiomyopathy. KEGG results showed that these genes were mainly involved in MAPK signaling pathway for ischemic cardiomyopathy and PI3K-Akt signaling pathway for idiopathic cardiomyopathy. We generated a co-expression network for hub genes and obtained top 10 medications suggested respectively for ischemic/idiopathic cardiomyopathy. Our study reveals the potential role of ferroptosis related genes in ischemic and idiopathic cardiomyopathy through bioinformatics analysis. The hub genes and potential drugs may become novel biomarkers for prognosis and precision treatment in the future.

摘要

铁死亡是最近发现的一种新的细胞死亡形式,不同于凋亡、坏死和自噬。本文期望通过筛选与铁死亡相关的潜在药物靶点,为未来心肌病的治疗提供新方向。使用GEO2R工具对来自基因表达综合数据库(GEO)的GSE5406进行差异表达分析。还对铁死亡相关基因进行了功能注释。然后我们构建了蛋白质-蛋白质相互作用网络,并使用Cytoscape鉴定了枢纽基因。通过cMap筛选靶向枢纽基因的药理化合物候选物。发现缺血性心肌病共有15个铁死亡相关基因(4个上调和11个下调),特发性心肌病有17个铁死亡相关基因(13个上调和4个下调)。这些基因涉及的生物学过程主要包括缺血性心肌病的凋亡过程负调控、类黄酮代谢过程、对药物的反应以及细胞对成纤维细胞生长因子刺激的反应,特发性心肌病的凋亡过程负调控以及对药物的反应。KEGG结果表明,这些基因在缺血性心肌病中主要参与MAPK信号通路,在特发性心肌病中主要参与PI3K-Akt信号通路。我们生成了枢纽基因的共表达网络,并分别获得了针对缺血性/特发性心肌病建议的前10种药物。我们的研究通过生物信息学分析揭示了铁死亡相关基因在缺血性和特发性心肌病中的潜在作用。枢纽基因和潜在药物可能成为未来预后和精准治疗的新型生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af6a/8927736/e0bb57916739/fcell-10-817819-g001.jpg

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