目的:讨论Rspo3基因在乳腺癌组织中的表达情况,启动子甲基化水平及意义。方法:通过The Human Protein Atlas分析Rspo3蛋白在乳腺癌组织中的表达情况;利用Oncomine、GEPIA、UALCAN数据库分析Rspo3 DNA、mRNA在乳腺癌组织中的表达情况;利...目的:讨论Rspo3基因在乳腺癌组织中的表达情况,启动子甲基化水平及意义。方法:通过The Human Protein Atlas分析Rspo3蛋白在乳腺癌组织中的表达情况;利用Oncomine、GEPIA、UALCAN数据库分析Rspo3 DNA、mRNA在乳腺癌组织中的表达情况;利用MethHC和UALCAN数据库分析Rspo3基因启动子区域甲基化水平;利用String-DB分析与Rspo3相互作用的蛋白。结果:在蛋白水平上,Rspo3蛋白在乳腺癌组织中较正常乳腺组织低表达,在DNA、mRNA水平上,Rspo3在乳腺癌组织中较正常乳腺组织显著低表达,且其启动子甲基化水平则显著增高。与Rspo3相关蛋白有LGR(4~6)、UBA52、UBB、UBC、Rspo1、Rspo4、ZNRF3、RNF43,可能调节乳腺癌中Wnt/β-catenin信号传导通路的激活。结论:基于现有的肿瘤数据库进行生物信息学分析,可以发现Rspo3在乳腺癌组织中呈低表达,其启动子甲基化水平则表达增高。这为深入研究乳腺癌,并发现新的乳腺肿瘤标志物提供了大样本数据支持。展开更多
As evolutionarily conserved signals,roof plate-specific spondins(R-spondins;RSPOs)are a family with four members(RSPO1e4)exerting distinctly different functions.RSPOs have five receptors and correlate with different s...As evolutionarily conserved signals,roof plate-specific spondins(R-spondins;RSPOs)are a family with four members(RSPO1e4)exerting distinctly different functions.RSPOs have five receptors and correlate with different signaling pathways through these receptors and then perform various functions.Moreover,their best-known molecular function is the capacity to enhance WNT signaling pathways,which play critical roles in several processes.A recent study shows that RSPOs not only potentiate the WNT/beta(b)-catenin signaling pathway but are also involved in the WNT/planar cell polarity signaling pathway.RSPOs influence liver homeostasis and the development of multiple liver diseases.RSPO1 increases cell proliferation,protects hepatocytes from injury,improves liver regenerative potential,and affects liver metabolic zonation.RSPO2 not only regulates proliferation-associated genes and promotes differentiation in the liver but also participates in liver fibrosis through the WNT/b-catenin signaling pathway.RSPO3 is a key determinant of proper liver function,such as promoting hepatocyte regeneration and maintaining liver zonation.RSPO3 is upregulated in liver fibrosis and livers of patients with nonalcoholic steatohepatitis.Besides,RSPO2 and RSPO3 are confirmed as oncogenes and involved in the occurrence of liver cancer.The role of RSPO4 in the liver remains unclear.In this review,the structural and biochemical properties of RSPOs and their receptors and their roles in liver homeostasis and disease are summarized.展开更多
文摘目的探讨R-spondin3(RSPO3)在乳腺癌中的表达及预后价值。方法应用TIMER、癌症基因组图谱(The Cancer Genome Atlas,TCGA)、基因表达谱数据动态分析(gene expression profilling in-teractive analysis 2,GEPIA2)、人类蛋白质表达图谱(Human Protein Atlas,HPA)等数据库分析RSPO3在乳腺癌组织和癌周正常组织中的差异表达,并分析其表达水平与乳腺癌病理学参数之间的相关性;GEPIA2数据库探讨RSPO3转录本在乳腺癌中的表达及其结构特征;Kaplan-Meier Plotter绘制RSPO3与乳腺癌患者的预后生存曲线;运用基因本体论(gene ontology,GO)和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)等对其进行基因功能富集分析和代谢通路分析;应用TIMER数据库分析RSPO3的表达水平与肿瘤微环境中免疫细胞浸润的相关性。结果RSPO3在乳腺癌中呈低表达,且其表达水平与乳腺癌患者的年龄、肿瘤最大径、分子分型相关,在乳腺癌中低表达的RSPO3与患者的预后不良相关;GO功能富集分析显示,RSPO3相互作用的基因主要富集于免疫细胞及其受体等参与的生物学过程;免疫细胞浸润分析结果显示,RSPO3在乳腺癌组织中的表达水平与CD8^(+)T细胞、CD4^(+)T细胞、CD4^(+)记忆T细胞、巨噬细胞、B细胞等的浸润水平呈正相关,而与调节性T细胞(Treg细胞)的浸润水平呈负相关;KEGG代谢通路分析显示,RSPO3可能参与Wnt/β-catenin通路。结论在乳腺癌中低表达的RSPO3与患者的不良预后相关,其可能通过抑制免疫细胞浸润及活化Wnt/β-catenin通路参与乳腺癌的进展。
文摘目的:讨论Rspo3基因在乳腺癌组织中的表达情况,启动子甲基化水平及意义。方法:通过The Human Protein Atlas分析Rspo3蛋白在乳腺癌组织中的表达情况;利用Oncomine、GEPIA、UALCAN数据库分析Rspo3 DNA、mRNA在乳腺癌组织中的表达情况;利用MethHC和UALCAN数据库分析Rspo3基因启动子区域甲基化水平;利用String-DB分析与Rspo3相互作用的蛋白。结果:在蛋白水平上,Rspo3蛋白在乳腺癌组织中较正常乳腺组织低表达,在DNA、mRNA水平上,Rspo3在乳腺癌组织中较正常乳腺组织显著低表达,且其启动子甲基化水平则显著增高。与Rspo3相关蛋白有LGR(4~6)、UBA52、UBB、UBC、Rspo1、Rspo4、ZNRF3、RNF43,可能调节乳腺癌中Wnt/β-catenin信号传导通路的激活。结论:基于现有的肿瘤数据库进行生物信息学分析,可以发现Rspo3在乳腺癌组织中呈低表达,其启动子甲基化水平则表达增高。这为深入研究乳腺癌,并发现新的乳腺肿瘤标志物提供了大样本数据支持。
基金This work was supported by grants from the Scientific Research Common Program of Beijing Municipal Commission of Education(No.KM202010025029)the National Natural Science Foundation of China(No.82070623 and 81970532)the Beijing Natural Science Foundation(No.7202007).
文摘As evolutionarily conserved signals,roof plate-specific spondins(R-spondins;RSPOs)are a family with four members(RSPO1e4)exerting distinctly different functions.RSPOs have five receptors and correlate with different signaling pathways through these receptors and then perform various functions.Moreover,their best-known molecular function is the capacity to enhance WNT signaling pathways,which play critical roles in several processes.A recent study shows that RSPOs not only potentiate the WNT/beta(b)-catenin signaling pathway but are also involved in the WNT/planar cell polarity signaling pathway.RSPOs influence liver homeostasis and the development of multiple liver diseases.RSPO1 increases cell proliferation,protects hepatocytes from injury,improves liver regenerative potential,and affects liver metabolic zonation.RSPO2 not only regulates proliferation-associated genes and promotes differentiation in the liver but also participates in liver fibrosis through the WNT/b-catenin signaling pathway.RSPO3 is a key determinant of proper liver function,such as promoting hepatocyte regeneration and maintaining liver zonation.RSPO3 is upregulated in liver fibrosis and livers of patients with nonalcoholic steatohepatitis.Besides,RSPO2 and RSPO3 are confirmed as oncogenes and involved in the occurrence of liver cancer.The role of RSPO4 in the liver remains unclear.In this review,the structural and biochemical properties of RSPOs and their receptors and their roles in liver homeostasis and disease are summarized.
