目的:分析泛素偶联酶E2C(ubiquitin conjugating enzyme E2C,UBE2C)在肺腺癌(lung adenocarcinoma,LUAD)中的表达及其临床意义。方法:通过癌症和基因肿瘤图谱(the Cancer Genome Atlas,TCGA)数据库、Oncomine数据库、人类蛋白质图谱(hum...目的:分析泛素偶联酶E2C(ubiquitin conjugating enzyme E2C,UBE2C)在肺腺癌(lung adenocarcinoma,LUAD)中的表达及其临床意义。方法:通过癌症和基因肿瘤图谱(the Cancer Genome Atlas,TCGA)数据库、Oncomine数据库、人类蛋白质图谱(human protein atlas,HPA)数据库分析UBE2C在LUAD组织和正常肺组织中mRNA和蛋白质表达水平的差异。采用受试者工作特征(receiver operating characteristic,ROC)曲线分析评估UBE2C诊断LUAD的价值。通过TCGA、国际癌症基因组联盟(International Cancer Genome Consortium,ICGC)数据库、cbioPortal数据库研究UBE2C表达与LUAD患者临床病理特征和预后的关系。通过基因集富集分析(gene set enrichment analysis,GSEA)分析UBE2C参与LUAD发生和发展的可能通路。结果:LUAD组织中UBE2C mRNA表达水平显著高于正常肺组织(P<0.01),其表达水平与TNM分期、N分期正相关(均P<0.05);与正常肺组织相比,UBE2C蛋白在LUAD组织中表达水平升高(P<0.01)。ROC曲线分析结果显示:UBE2C诊断LUAD的AUC值为0.969(95%CI:0.953~0.984,P<0.01)。UBE2C的表达水平与TNM分期有关(P<0.05)。UBE2C表达高低与年龄、性别、TNM分期、T分期及N分期有关(均P<0.05),且UBE2C高表达组病死率较低表达组高(95/247 vs 68/248,P=0.009)。生存分析结果显示:UBE2C高表达组LUAD患者总生存率(overall survival,OS)显著低于低表达组(P<0.05)。发生UBE2C改变的LUAD患者其OS低于未发生改变者(P<0.01)。UBE2C高表达富集在与细胞周期、P53信号通路、DNA错配修复、DNA复制等通路相关的基因集(均P<0.01)。结论:UBE2C在LUAD组织中表达显著上调,其高表达或发生基因改变提示LUAD患者预后差,UBE2C可作为一个潜在的LUAD分子诊断标志物,是LUAD治疗的潜在靶点。展开更多
Ubiquitination is emerging as a tight regulatory mechanism that is necessary for all aspects of development and survival of all eukaryotes. Recent genomic and genetic analysis in Arabidopsis suggests that ubiquitinati...Ubiquitination is emerging as a tight regulatory mechanism that is necessary for all aspects of development and survival of all eukaryotes. Recent genomic and genetic analysis in Arabidopsis suggests that ubiquitination may also play important roles in plant response to the phytohormone abscisic acid （ABA）. Many components of the ubiquitination pathway, such as ubiquitin-conjugating enzyme E2, ubiquitin ligase E3 and components of the proteasome, have been identified or predicted to be essential in ABA biosynthesis, catabolism and signaling. In addition, the ubiquitination-related pathway, sumoylation, is also involved in ABA signaling. We summarize in this report recent developments to elucidate their roles in the ABA-related pathway.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is now the most common primary liver malignancy worldwide,and multiple risk factors attribute to the occurrence and development of HCC.Recently,increasing studies suggest that u...BACKGROUND Hepatocellular carcinoma(HCC)is now the most common primary liver malignancy worldwide,and multiple risk factors attribute to the occurrence and development of HCC.Recently,increasing studies suggest that ubiquitinconjugating enzyme E2T(UBE2T)serves as a promising prognostic factor in human cancers,although the molecular mechanism of UBE2T in HCC remains unclear.AIM To investigate the clinical relevance and role of UBE2T in HCC development.METHODS UBE2T expression in HCC tissues from the TCGA database and its association with patient survival were analyzed.A lentivirus-mediated strategy was used to knock down UBE2T in HCC cells.qRT-PCR and Western blot assays were performed to check the effect of UBE2T silencing in HCC cells.Cell growth in vitro and in vivo was analyzed by multiparametric high-content screening and the xenograft tumorigenicity assay,respectively.Cell cycle distribution and apoptosis were determined by flow cytometry.The genes regulated by UBE2T were profiled by microarray assay.RESULTS UBE2T was overexpressed in HCC tissues compared with paired and non-paired normal tissues.High expression of UBE2T predicted a poor overall survival in HCC patients.In vitro,lentivirus-mediated UBE2T knockdown significantly reduced the viability of both SMMC-7721 and BEL-7404 cells.In vivo,the xenograft tumorigenesis of SMMC-7721 cells was largely attenuated by UBE2T silencing.The cell cycle was arrested at G1/S phase in SMMC-7721 and BEL-7404 cells with UBE2T knockdown.Furthermore,apoptosis was increased by UBE2T knockdown.At the molecular level,numerous genes were dysregulated after UBE2T silencing,including IL-1B,FOSL1,PTGS2,and BMP6.CONCLUSION UBE2T plays an important role in cell cycle progression,apoptosis,and HCC development.展开更多
文摘目的:分析泛素偶联酶E2C(ubiquitin conjugating enzyme E2C,UBE2C)在肺腺癌(lung adenocarcinoma,LUAD)中的表达及其临床意义。方法:通过癌症和基因肿瘤图谱(the Cancer Genome Atlas,TCGA)数据库、Oncomine数据库、人类蛋白质图谱(human protein atlas,HPA)数据库分析UBE2C在LUAD组织和正常肺组织中mRNA和蛋白质表达水平的差异。采用受试者工作特征(receiver operating characteristic,ROC)曲线分析评估UBE2C诊断LUAD的价值。通过TCGA、国际癌症基因组联盟(International Cancer Genome Consortium,ICGC)数据库、cbioPortal数据库研究UBE2C表达与LUAD患者临床病理特征和预后的关系。通过基因集富集分析(gene set enrichment analysis,GSEA)分析UBE2C参与LUAD发生和发展的可能通路。结果:LUAD组织中UBE2C mRNA表达水平显著高于正常肺组织(P<0.01),其表达水平与TNM分期、N分期正相关(均P<0.05);与正常肺组织相比,UBE2C蛋白在LUAD组织中表达水平升高(P<0.01)。ROC曲线分析结果显示:UBE2C诊断LUAD的AUC值为0.969(95%CI:0.953~0.984,P<0.01)。UBE2C的表达水平与TNM分期有关(P<0.05)。UBE2C表达高低与年龄、性别、TNM分期、T分期及N分期有关(均P<0.05),且UBE2C高表达组病死率较低表达组高(95/247 vs 68/248,P=0.009)。生存分析结果显示:UBE2C高表达组LUAD患者总生存率(overall survival,OS)显著低于低表达组(P<0.05)。发生UBE2C改变的LUAD患者其OS低于未发生改变者(P<0.01)。UBE2C高表达富集在与细胞周期、P53信号通路、DNA错配修复、DNA复制等通路相关的基因集(均P<0.01)。结论:UBE2C在LUAD组织中表达显著上调,其高表达或发生基因改变提示LUAD患者预后差,UBE2C可作为一个潜在的LUAD分子诊断标志物,是LUAD治疗的潜在靶点。
基金Supported by the Ministry of Science and Technology of China （863- 2002AA224111）, the State Key Development Program of Basic Research of China （973-2003CB114304）, the National Natural Science Foundation of China （30325030 and 30530400） and the Knowledge Innovation Project of the Chinese Academy of Sciences. Publication of this paper is supported by the National Natural Science Foundation of China （30624808） and Science Publication Foundation of the Chinese Academy of Sciences.
文摘Ubiquitination is emerging as a tight regulatory mechanism that is necessary for all aspects of development and survival of all eukaryotes. Recent genomic and genetic analysis in Arabidopsis suggests that ubiquitination may also play important roles in plant response to the phytohormone abscisic acid （ABA）. Many components of the ubiquitination pathway, such as ubiquitin-conjugating enzyme E2, ubiquitin ligase E3 and components of the proteasome, have been identified or predicted to be essential in ABA biosynthesis, catabolism and signaling. In addition, the ubiquitination-related pathway, sumoylation, is also involved in ABA signaling. We summarize in this report recent developments to elucidate their roles in the ABA-related pathway.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is now the most common primary liver malignancy worldwide,and multiple risk factors attribute to the occurrence and development of HCC.Recently,increasing studies suggest that ubiquitinconjugating enzyme E2T(UBE2T)serves as a promising prognostic factor in human cancers,although the molecular mechanism of UBE2T in HCC remains unclear.AIM To investigate the clinical relevance and role of UBE2T in HCC development.METHODS UBE2T expression in HCC tissues from the TCGA database and its association with patient survival were analyzed.A lentivirus-mediated strategy was used to knock down UBE2T in HCC cells.qRT-PCR and Western blot assays were performed to check the effect of UBE2T silencing in HCC cells.Cell growth in vitro and in vivo was analyzed by multiparametric high-content screening and the xenograft tumorigenicity assay,respectively.Cell cycle distribution and apoptosis were determined by flow cytometry.The genes regulated by UBE2T were profiled by microarray assay.RESULTS UBE2T was overexpressed in HCC tissues compared with paired and non-paired normal tissues.High expression of UBE2T predicted a poor overall survival in HCC patients.In vitro,lentivirus-mediated UBE2T knockdown significantly reduced the viability of both SMMC-7721 and BEL-7404 cells.In vivo,the xenograft tumorigenesis of SMMC-7721 cells was largely attenuated by UBE2T silencing.The cell cycle was arrested at G1/S phase in SMMC-7721 and BEL-7404 cells with UBE2T knockdown.Furthermore,apoptosis was increased by UBE2T knockdown.At the molecular level,numerous genes were dysregulated after UBE2T silencing,including IL-1B,FOSL1,PTGS2,and BMP6.CONCLUSION UBE2T plays an important role in cell cycle progression,apoptosis,and HCC development.
