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pmid:40269003
CDC6 as early biomarker for myocardial infarction with acute cellular senescence and repair mechanisms.
Yun Wen · Xiaofang Zhang · Jiaxin Wang · Caixia Ma · Liangyan Wu · Lihong Wang
Scientific reports · 2025 doi:10.1038/s41598-025-94988-x
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Complete file
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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. 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