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...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。展开更多
Background: Centrosomal protein 78(CEP78) has been characterized as a component of the centrosome required for the regulation of centrosome-related events during the cell cycle, but its role in human cancers remains u...Background: Centrosomal protein 78(CEP78) has been characterized as a component of the centrosome required for the regulation of centrosome-related events during the cell cycle, but its role in human cancers remains unclear. This study aimed to investigate the role and the clinical value of CEP78 in colorectal cancer(CRC).Methods: Quantitative real-time polymerase chain reaction(q RT-PCR) and immunohistochemistry were performed to examine CEP78 expression in CRC tissues and adjacent noncancerous tissues. The association between CEP78 expression and clinical outcomes of CRC patients was determined. The effect of CEP78 on cell growth was examined in vitro by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide(MTT) assay, colony formation, and flow cytometry assays and in vivo using a nude mouse model.Results: The expression level of CEP78 was significantly lower in tumor tissues than in the adjacent normal tissues(P < 0.01). Low CEP78 expression was significantly associated with poor differentiation(P etastasis(P = 0.003), large tumor size(P = 0.017), lymphatic mtient= 0.034), distant metastasis(P s with low CEP78 expression h= 0.029), and advanced stage(P Meier analysis indicated that paad shorter survival than those wit= 0.011). Kaplan–h high CEP78 expression(P < 0.01). Overexpression of CEP78 in CRC cells significantly reduced cell viability and colony formation in vitro and halted tumor growth in vivo. Further study showed that CEP78 reintroduction in CRC cells resulted in G2/M phase arrest rather than cell apoptosis.Conclusions: CEP78 might function as a tumor suppressor and serve as a novel prognostic marker in CRC.展开更多
文摘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。
文摘Background: Centrosomal protein 78(CEP78) has been characterized as a component of the centrosome required for the regulation of centrosome-related events during the cell cycle, but its role in human cancers remains unclear. This study aimed to investigate the role and the clinical value of CEP78 in colorectal cancer(CRC).Methods: Quantitative real-time polymerase chain reaction(q RT-PCR) and immunohistochemistry were performed to examine CEP78 expression in CRC tissues and adjacent noncancerous tissues. The association between CEP78 expression and clinical outcomes of CRC patients was determined. The effect of CEP78 on cell growth was examined in vitro by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide(MTT) assay, colony formation, and flow cytometry assays and in vivo using a nude mouse model.Results: The expression level of CEP78 was significantly lower in tumor tissues than in the adjacent normal tissues(P < 0.01). Low CEP78 expression was significantly associated with poor differentiation(P etastasis(P = 0.003), large tumor size(P = 0.017), lymphatic mtient= 0.034), distant metastasis(P s with low CEP78 expression h= 0.029), and advanced stage(P Meier analysis indicated that paad shorter survival than those wit= 0.011). Kaplan–h high CEP78 expression(P < 0.01). Overexpression of CEP78 in CRC cells significantly reduced cell viability and colony formation in vitro and halted tumor growth in vivo. Further study showed that CEP78 reintroduction in CRC cells resulted in G2/M phase arrest rather than cell apoptosis.Conclusions: CEP78 might function as a tumor suppressor and serve as a novel prognostic marker in CRC.
