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作 者:季沙 雷建东[1] 吴林军[1] 蒋志敏[1] 王思入 JI Sha;LEI Jiandong;WU Linjun;JIANG Zhimin;WANG Siru(Department of Laboratory,Leshan Traditional Chinese Medicine Hospital,Leshan 614000,Sichuan,China)
出 处:《中国分子心脏病学杂志》2025年第1期6615-6622,共8页Molecular Cardiology of China
摘 要:目的探讨中心体蛋白78(centrosomal protein 78,CEP78)对内皮细胞生物学行为的影响及其与冠心病(coronary heart disease,CHD)的关系。方法通过Gene Expression Omnibus(GEO)数据库检索CHD相关数据集,利用StataSE 15求CEP78的总标准化平均差(standardized mean difference,SMD)并绘制总受试者操作特征(summary receiver operating characteristic,SROC)曲线。利用单细胞RNA测序分析CEP78在不同细胞中的表达情况。在人脐静脉内皮细胞株(EA.hy926)中构建过表达CEP78(OE_CEP78)和过表达空载质粒(OE_NC)模型,通过细胞划痕、Transwell、CCK8和细胞凋亡实验验证CEP78和CHD之间的相关性。利用SMD和Spearman相关性分析求CEP78差异共表达基因,通过Metascape数据库对CEP78差异共表达基因进行基因本体(gene ontology,GO)和京都基因和基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)富集分析。结果CEP78在CHD中低表达(总SMD=-0.99,95%CI:-1.79~-0.20,P=0.015),SROC曲线下面积(area under the curve,AUC)为0.77(0.73~0.81),证明CEP78对CHD具有中等诊断能力。单细胞RNA测序分析结果显示,CEP78在正常外周血自然杀伤细胞中高表达。OE_CEP78可以抑制EA.hy926细胞的增殖、迁移和凋亡。KEGG通路富集分析显示CEP78差异正相关基因富集在FOXO信号通路。结论CEP78在CHD中低表达,对CHD具有中等诊断能力,并通过抑制内皮细胞的增殖、迁移和凋亡来抑制CHD的发生发展。Objective To investigate the effect of centrosomal protein 78(CEP78)on the biological behavior of endothelial cells and its relationship with coronary heart disease(CHD).Methods The data sets related to CHD were retrieved from the Gene Expression Omnibus(GEO)database.Stata/SE 15 was used to calculate the total standardized mean difference(SMD)of CEP78 and draw the summary receiver operating characteristic(SROC)curve.Single-cell RNA sequencing was used to analyze CEP78 expression in different cells.Overexpression of CEP78(OE_CEP78)and overexpression of empty plasmid(OE_NC)were constructed in human umbilical vein endothelial cells(EA.hy926).The correlation between CEP78 and CHD was verified by cell scratch,Transwell,Cell Counting Kit-8(CCK-8),and apoptosis experiments.SMD and spearman correlation analysis were used to find CEP78 differentially co-expressed genes,and Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis of CEP78 differentially co-expressed genes was performed through Metascape database.Results CEP78 was lowly expressed in CHD(total SMD=-0.99,95%CI:-1.79--0.20,P=0.015),and the area under the SROC curve was 0.77(0.73-0.81),which showed that CEP78 had moderate diagnostic performance for CHD.Single-cell RNA sequencing analysis showed that CEP78 was highly expressed in normal peripheral natural killer cells.OE_CEP78 can inhibit the proliferation,migration,and apoptosis of EA.hy926 cells.KEGG pathway enrichment analysis showed that CEP78 differentially positively co-expressed genes were enriched in the FOXO signaling pathway.Conclusions CEP78 was lowly expressed and demonstrated moderate diagnostic ability for CHD.CEP78 can inhibit the occurrence and development of CHD by inhibiting the proliferation,migration,and apoptosis of endothelial cells.
关 键 词:冠心病 内皮细胞 CEP78 单细胞RNA测序分析 凋亡
分 类 号:R541.4[医药卫生—心血管疾病]
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