Background:Small ubiquitin-like modifier(SUMO)-specific proteases(SENPs)cleave the isopeptidic bond between SUMO1/2/3 and protein substrates,thus regulating the structure,activity,and lifetime of a variety of proteins...Background:Small ubiquitin-like modifier(SUMO)-specific proteases(SENPs)cleave the isopeptidic bond between SUMO1/2/3 and protein substrates,thus regulating the structure,activity,and lifetime of a variety of proteins.Recently,accumulating evidence has suggested that SENPs play a role in the initiation and progression of human cancers.Nevertheless,the potential role of the SENP family of proteins in liver cancer has yet to be fully elucidated.Methods:This study conducted a comprehensive bioinformatics analysis of the SENP family in liver cancer,including differential expression profiling,survival analysis,mutation and copy number variations(CNVs)assessment,immune infiltration and drug sensitivity correlation,functional enrichment analyses using data from The Cancer Genome Atlas(TCGA),Clinical Proteomic Tumor Analysis Consortium(CPTAC),LinkedOmics,and other public databases.Furthermore,we performed in vitro experiments using Huh-7 and Hep-3B cell lines to investigate the functional roles of SENP1 and SENP3 in hepatocellular carcinoma cell proliferation,colony formation,and migration.Results:Our results indicated that SENP1,3,and 7 were significantly overexpressed in liver hepatocellular carcinoma(LIHC).Elevated expressions of SENP1,3,and 7 are positively correlated with poor overall survival(OS)in LIHC patients.In addition,SENP1,3,and 7 expressions are related to immune infiltration and drug sensitivity.SENP1,3,and 7 co-expressed genes were enriched in mitochondrial function,ribosomal translation,and cell cycle control.Conclusion:SENP1,3,and 7 are prognostic biomarkers and potential therapeutic targets for LIHC.Knockdown of SENP1 and SENP3 inhibited the proliferation,clonogenicity,and migration of hepatocellular carcinoma cells.展开更多
Objective SUMO-specific protease 3(SENP3),a member of the SUMO-specific protease family,reverses the SUMOylation of SUMO-2/3 conjugates.Dysregulation of SENP3 has been proven to be involved in the development of vario...Objective SUMO-specific protease 3(SENP3),a member of the SUMO-specific protease family,reverses the SUMOylation of SUMO-2/3 conjugates.Dysregulation of SENP3 has been proven to be involved in the development of various tumors.However,its role in mantle cell lymphoma(MCL),a highly aggressive lymphoma,remains unclear.This study was aimed to elucidate the effect of SENP3 in MCL.Methods The expression of SENP3 in MCL cells and tissue samples was detected by RT-qPCR,Western blotting or immunohistochemistry.MCL cells with stable SENP3 knockdown were constructed using short hairpin RNAs.Cell proliferation was assessed by CCK-8 assay,and cell apoptosis was determined by flow cytometry.mRNA sequencing(mRNA-seq)was used to investigate the underlying mechanism of SENP3 knockdown on MCL development.A xenograft nude mouse model was established to evaluate the effect of SENP3 on MCL growth in vivo.Results SENP3 was upregulated in MCL patient samples and cells.Knockdown of SENP3 in MCL cells inhibited cell proliferation and promoted cell apoptosis.Meanwhile,the canonical Wnt signaling pathway and the expression of Wnt10a were suppressed after SENP3 knockdown.Furthermore,the growth of MCL cells in vivo was significantly inhibited after SENP3 knockdown in a xenograft nude mouse model.Conclusion SENP3 participants in the development of MCL and may serve as a therapeutic target for MCL.展开更多
目的:探讨小泛素样修饰物特异的蛋白酶5(SUMO specific protease5,SENP5)在舌鳞状细胞癌中的表达及意义。方法:采用免疫组化方法对33例原发舌鳞癌及癌旁上皮中SENP5的表达进行检测。应用SPSS11.0软件包对免疫组化半定量检测结果与有关...目的:探讨小泛素样修饰物特异的蛋白酶5(SUMO specific protease5,SENP5)在舌鳞状细胞癌中的表达及意义。方法:采用免疫组化方法对33例原发舌鳞癌及癌旁上皮中SENP5的表达进行检测。应用SPSS11.0软件包对免疫组化半定量检测结果与有关临床特征和病理指标间的关系进行Wilcoxon检验和Spearman等级相关检验。另使用钙离子对人舌癌细胞系Tca8113进行诱导分化,实时定量PCR和细胞免疫化学检测SENP5的表达改变。结果:舌鳞癌中SENP5的表达高于癌旁上皮(P=0.000),表达水平与鳞癌的分化程度相关(P=0.022);钙离子诱导分化可使人舌癌细胞系Tca8113中SENP5的表达增加。结论:SENP5的表达水平与舌鳞癌的分化相关,提示其与肿瘤的发生、发展具有一定关系。展开更多
SUMO化修饰是一种把小泛素相关修饰物(small ubiquition related modifier,SUMO)共价连接到细胞内靶蛋白半胱氨酸残基上的一种蛋白质翻译后修饰。SUMO化修饰参与并调控着多种细胞进程,如转录调控、核转运和信号转导等。SUMO化修饰是一...SUMO化修饰是一种把小泛素相关修饰物(small ubiquition related modifier,SUMO)共价连接到细胞内靶蛋白半胱氨酸残基上的一种蛋白质翻译后修饰。SUMO化修饰参与并调控着多种细胞进程,如转录调控、核转运和信号转导等。SUMO化修饰是一种动态可逆的修饰方式。SUMO特异性蛋白酶(SUMO-specific proteases,SENPs)可以使SUMO化修饰的蛋白质发生去SUMO化,在维持细胞内SUMO化与去SUMO化的平衡中起重要作用。研究表明,SENPs与多种癌症的发生发展密切相关,如SENP1能直接调节多条致癌通路,诱发正常的前列腺上皮细胞状态异常。癌细胞中的SENP3能诱导血管生成。因此,对去SUMO化机制研究可以为开发癌症治疗药物提供新的思路。展开更多
目的初步探讨冠心康通过SENP1对巨噬细胞胞葬作用的影响和相关机制。方法采用慢病毒Lv-si-SENP1-RNAi感染RAW264.7巨噬细胞构建SENP1抑表达的巨噬细胞,以氧化低密度脂蛋白(oxidized low density lipoprotein,ox-LDL)损伤的RAW264.7细胞...目的初步探讨冠心康通过SENP1对巨噬细胞胞葬作用的影响和相关机制。方法采用慢病毒Lv-si-SENP1-RNAi感染RAW264.7巨噬细胞构建SENP1抑表达的巨噬细胞,以氧化低密度脂蛋白(oxidized low density lipoprotein,ox-LDL)损伤的RAW264.7细胞作为动脉粥样硬化巨噬细胞病理模型,给予冠心康干预。细胞分组:(1)RAW264.7细胞:对照组、模型组、冠心康低、中、高剂量组;(2)感染慢病毒后的细胞:si-ns-RAW264.7细胞和si-SENP1-RAW264.7细胞,均分别设置对照组、模型组、冠心康高剂量组。应用RT-qPCR、Western blot法检测胞葬相关信号分子mRNA和蛋白的表达水平。结果与RAW264.7对照组相比,模型组细胞CX3CR1、Mfge8、TIM4、C1qa蛋白表达降低(P<0.05),与模型组相比,冠心康上调CX3CR1、Mfge8、TIM4、C1qa蛋白表达(P<0.05)。与si-ns-RAW264.7对照组相比,si-SENP1-RAW264.7对照组CX3CR1、TIM4 mRNA含量和CX3CR1、Mfge8、TIM4、C1qa蛋白表达均降低(P<0.05);与si-ns-RAW264.7模型组相比,si-SENP1-RAW264.7模型组CX3CR1、Mfge8、TIM4蛋白表达降低(P<0.05);与si-ns-RAW264.7高剂量组相比,si-SENP1-RAW264.7高剂量组Mfge8、TIM4、C1qa蛋白表达降低(P<0.05)。结论冠心康可能通过SENP1调控巨噬细胞胞葬作用,减轻ox-LDL诱导的巨噬细胞损伤。展开更多
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.32070616 and 82170794).
文摘Background:Small ubiquitin-like modifier(SUMO)-specific proteases(SENPs)cleave the isopeptidic bond between SUMO1/2/3 and protein substrates,thus regulating the structure,activity,and lifetime of a variety of proteins.Recently,accumulating evidence has suggested that SENPs play a role in the initiation and progression of human cancers.Nevertheless,the potential role of the SENP family of proteins in liver cancer has yet to be fully elucidated.Methods:This study conducted a comprehensive bioinformatics analysis of the SENP family in liver cancer,including differential expression profiling,survival analysis,mutation and copy number variations(CNVs)assessment,immune infiltration and drug sensitivity correlation,functional enrichment analyses using data from The Cancer Genome Atlas(TCGA),Clinical Proteomic Tumor Analysis Consortium(CPTAC),LinkedOmics,and other public databases.Furthermore,we performed in vitro experiments using Huh-7 and Hep-3B cell lines to investigate the functional roles of SENP1 and SENP3 in hepatocellular carcinoma cell proliferation,colony formation,and migration.Results:Our results indicated that SENP1,3,and 7 were significantly overexpressed in liver hepatocellular carcinoma(LIHC).Elevated expressions of SENP1,3,and 7 are positively correlated with poor overall survival(OS)in LIHC patients.In addition,SENP1,3,and 7 expressions are related to immune infiltration and drug sensitivity.SENP1,3,and 7 co-expressed genes were enriched in mitochondrial function,ribosomal translation,and cell cycle control.Conclusion:SENP1,3,and 7 are prognostic biomarkers and potential therapeutic targets for LIHC.Knockdown of SENP1 and SENP3 inhibited the proliferation,clonogenicity,and migration of hepatocellular carcinoma cells.
基金supported by the Chongqing Natural Science Foundation(No.2023NSCQ-MSX3161 and No.cstc2020jcyj-msxmX1058)the National Natural Science Foundation of China(No.81800172).
文摘Objective SUMO-specific protease 3(SENP3),a member of the SUMO-specific protease family,reverses the SUMOylation of SUMO-2/3 conjugates.Dysregulation of SENP3 has been proven to be involved in the development of various tumors.However,its role in mantle cell lymphoma(MCL),a highly aggressive lymphoma,remains unclear.This study was aimed to elucidate the effect of SENP3 in MCL.Methods The expression of SENP3 in MCL cells and tissue samples was detected by RT-qPCR,Western blotting or immunohistochemistry.MCL cells with stable SENP3 knockdown were constructed using short hairpin RNAs.Cell proliferation was assessed by CCK-8 assay,and cell apoptosis was determined by flow cytometry.mRNA sequencing(mRNA-seq)was used to investigate the underlying mechanism of SENP3 knockdown on MCL development.A xenograft nude mouse model was established to evaluate the effect of SENP3 on MCL growth in vivo.Results SENP3 was upregulated in MCL patient samples and cells.Knockdown of SENP3 in MCL cells inhibited cell proliferation and promoted cell apoptosis.Meanwhile,the canonical Wnt signaling pathway and the expression of Wnt10a were suppressed after SENP3 knockdown.Furthermore,the growth of MCL cells in vivo was significantly inhibited after SENP3 knockdown in a xenograft nude mouse model.Conclusion SENP3 participants in the development of MCL and may serve as a therapeutic target for MCL.
文摘目的:探讨小泛素样修饰物特异的蛋白酶5(SUMO specific protease5,SENP5)在舌鳞状细胞癌中的表达及意义。方法:采用免疫组化方法对33例原发舌鳞癌及癌旁上皮中SENP5的表达进行检测。应用SPSS11.0软件包对免疫组化半定量检测结果与有关临床特征和病理指标间的关系进行Wilcoxon检验和Spearman等级相关检验。另使用钙离子对人舌癌细胞系Tca8113进行诱导分化,实时定量PCR和细胞免疫化学检测SENP5的表达改变。结果:舌鳞癌中SENP5的表达高于癌旁上皮(P=0.000),表达水平与鳞癌的分化程度相关(P=0.022);钙离子诱导分化可使人舌癌细胞系Tca8113中SENP5的表达增加。结论:SENP5的表达水平与舌鳞癌的分化相关,提示其与肿瘤的发生、发展具有一定关系。
文摘SUMO化修饰是一种把小泛素相关修饰物(small ubiquition related modifier,SUMO)共价连接到细胞内靶蛋白半胱氨酸残基上的一种蛋白质翻译后修饰。SUMO化修饰参与并调控着多种细胞进程,如转录调控、核转运和信号转导等。SUMO化修饰是一种动态可逆的修饰方式。SUMO特异性蛋白酶(SUMO-specific proteases,SENPs)可以使SUMO化修饰的蛋白质发生去SUMO化,在维持细胞内SUMO化与去SUMO化的平衡中起重要作用。研究表明,SENPs与多种癌症的发生发展密切相关,如SENP1能直接调节多条致癌通路,诱发正常的前列腺上皮细胞状态异常。癌细胞中的SENP3能诱导血管生成。因此,对去SUMO化机制研究可以为开发癌症治疗药物提供新的思路。
