Wen Yun, Zhang Xiaofang, Wang Jiaxin, Ma Caixia, Wu Liangyan, Wang Lihong
Department of Endocrinology and Metabolism, First Affiliated Hospital of Jinan University, Guangzhou, China.
The Academician Cooperative Laboratory of Basic and Translational Research on Chronic Diseases, The First Affiliated Hospital, Jinan University, Guangzhou, China.
Sci Rep. 2025 Apr 23;15(1):14130. doi: 10.1038/s41598-025-94988-x.
We aimed to the exploration of genes related to the cell cycle and the mechanisms of cardiac cell repair and senescence post-MI. The sequencing dataset of myocardial infarction in mice (GSE161427) was downloaded from the Gene Expression Omnibus (GEO) database, yielding 894 upregulated differentially expressed genes (DEGsup). Additionally, 494 senescence-related genes (SRGs) were obtained from the CellAge database. The overlapping differentially expressed genes (DEupSGs) between these two sets were identified using the R software. WGCNA using the GSE59867 dataset revealed a highly related module to MI. The intersection of core genes from the purple module and DEupSGs yielded 12 genes. Through machine learning and PPI analysis, two target genes related to MI and cellular senescence were identified: CDC6 and PLK1. ROC curve analysis using the MI animal myocardial sample dataset GSE775 and the patient blood sample dataset GSE60993 indicated that CDC6 expression has high diagnostic value for MI and cellular senescence, with differential expression levels at various times post-infarction.These results show that CDC6 is specifically upregulated in the early stages of MI, and both in vivo and ex vivo model results are consistent with bioinformatics findings. Additionally, overexpression of CDC6 in the early oxygen-glucose deprivation (OGD) model in vitro increased the expression of genes mediating cardiac repair. Interestingly, when ABT263 was used to clear senescent cells, the expression of genes mediating repair in primary cardiac cells decreased, suggesting that acute ischemic hypoxia early on, CDC6-mediated acute cardiac cell senescence may promote early cardiac repair. This finding may provide new insights into the monitoring and assessment of cardiac cell senescence and repair in the early stages of MI.
我们旨在探索与细胞周期相关的基因以及心肌梗死后心脏细胞修复和衰老的机制。从小鼠心肌梗死的测序数据集（GSE161427）下载自基因表达综合数据库（GEO），得到894个上调的差异表达基因（DEGsup）。此外，从CellAge数据库中获得了494个衰老相关基因（SRGs）。使用R软件鉴定了这两组之间的重叠差异表达基因（DEupSGs）。使用GSE59867数据集的加权基因共表达网络分析（WGCNA）揭示了一个与心肌梗死高度相关的模块。紫色模块的核心基因与DEupSGs的交集产生了12个基因。通过机器学习和蛋白质-蛋白质相互作用（PPI）分析，鉴定出两个与心肌梗死和细胞衰老相关的靶基因：细胞分裂周期蛋白6（CDC6）和极光激酶1（PLK1）。使用心肌梗死动物心肌样本数据集GSE775和患者血液样本数据集GSE60993进行的受试者工作特征（ROC）曲线分析表明，CDC6表达对心肌梗死和细胞衰老具有较高的诊断价值，在梗死后不同时间点表达水平存在差异。这些结果表明，CDC6在心肌梗死早期特异性上调，体内和体外模型结果均与生物信息学研究结果一致。此外，在体外早期氧糖剥夺（OGD）模型中过表达CDC6可增加介导心脏修复的基因的表达。有趣的是，当使用ABT263清除衰老细胞时，原代心脏细胞中介导修复的基因的表达下降，这表明在急性缺血缺氧早期，CDC6介导的急性心脏细胞衰老可能促进早期心脏修复。这一发现可能为心肌梗死早期心脏细胞衰老和修复的监测与评估提供新的见解。
