Deparment of Cardiology, The First Affiliated Hospital of Hainan Medical University, Haikou, 570100, China.
Hainan Provincial Key Laboratory of Tropical Brain Research and Transformation, Hainan Medical University, Haikou, 570100, China.
BMC Cardiovasc Disord. 2022 Jul 29;22(1):339. doi: 10.1186/s12872-022-02747-x.
Coronary atherosclerosis (CA) is the most common type of atherosclerosis. However, the inherent pathogenesis and mechanisms of CA are unclear, and the relationship with ferroptosis-related genes (FRGs) has not been reported. The purpose of this study was to use bioinformatics techniques to evaluate potential therapeutic targets for CA.Please provide the given name for author "Dingshun".Please provide the given name for author "Dingshun".
First, the GSE132651 dataset was acquired from the Gene Expression Omnibus database. Gene Ontology enrichment analysis, Kyoto Encyclopedia of Genes and Genomes enrichment analysis, and Protein-Protein interaction network were successively conducted. Next, overlapping genes between hub genes and CA genes were found. FRGs were found when comparing the CA group with the normal group. The correlation between overlapping genes and FRGs was further analyzed. At last, we performed Elisa to validate the expression of these genes in human blood specimens. Mice aortic tissues were used for western blot to detect the expression of proteins.
Based on the GSE132651 dataset, 102 differentially expressed genes were identified. Five overlapping genes between hub genes and CA genes were found (CCNA2, RRM2, PBK, PCNA, CDK1). TFRC and GPX4 were found to be FRGs. TFRC was positively correlated with CCNA2, PBK, PCNA, CDK1, RRM2, with CDK1 being the strongest correlation. GPX4 was negatively correlated with these genes, among which CCNA2 was the strongest correlation. The ELISA results showed that CCNA2, CDK1, and TFRC expression were markedly increased in serum of the CA samples compared with controls, while GPX4 expression was markedly decreased in the CA samples. The western blot results show that GPX4 expression was lower in the model group, TFRC, CDK1, and CCNA2 protein expression were high in the model group.
Ferroptosis-related genes GPX4 and TFRC were closely correlated with the identified overlapping genes CCNA2 and CDK1, which may serve as targeted therapies for the treatment of CA.
冠状动脉粥样硬化（CA）是最常见的动脉粥样硬化类型。然而，CA 的内在发病机制和机制尚不清楚，与铁死亡相关基因（FRGs）的关系尚未报道。本研究旨在利用生物信息学技术评估 CA 的潜在治疗靶点。
首先从基因表达综合数据库中获取 GSE132651 数据集。依次进行基因本体论富集分析、京都基因与基因组百科全书富集分析和蛋白质-蛋白质相互作用网络分析。接着，找到枢纽基因和 CA 基因之间的重叠基因。将 CA 组与正常组进行比较，找到 FRGs。进一步分析重叠基因与 FRGs 之间的相关性。最后，我们使用 ELISA 验证这些基因在人血标本中的表达情况。使用小鼠主动脉组织进行 Western blot 检测蛋白表达。
基于 GSE132651 数据集，鉴定出 102 个差异表达基因。发现 5 个枢纽基因和 CA 基因之间的重叠基因（CCNA2、RRM2、PBK、PCNA、CDK1）。发现 TFRC 和 GPX4 是 FRGs。TFRC 与 CCNA2、PBK、PCNA、CDK1、RRM2 呈正相关，其中与 CDK1 的相关性最强。GPX4 与这些基因呈负相关，其中与 CCNA2 的相关性最强。ELISA 结果显示，与对照组相比，CA 样本血清中 CCNA2、CDK1 和 TFRC 的表达明显增加，而 GPX4 的表达明显降低。Western blot 结果显示模型组中 GPX4 表达较低，模型组中 TFRC、CDK1 和 CCNA2 蛋白表达较高。
铁死亡相关基因 GPX4 和 TFRC 与鉴定出的重叠基因 CCNA2 和 CDK1 密切相关，它们可能作为 CA 治疗的靶向治疗。
