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
The Myc gene is the essential oncogene in triple-negative breast cancer(TNBC).This study investigates the synergistic effects of combining Myc decoy oligodeoxynucleotides-encapsulated niosomes-selenium hybrid nanocarr...The Myc gene is the essential oncogene in triple-negative breast cancer(TNBC).This study investigates the synergistic effects of combining Myc decoy oligodeoxynucleotides-encapsulated niosomes-selenium hybrid nanocarriers with X-irradiation exposure on the MDA-MB-468 cell line.Decoy and scramble ODNs for Myc transcription factor were designed and synthesized based on promoter sequences of the Bcl2 gene.The nanocarriers were synthesized by loading Myc ODNs and selenium into chitosan(Chi-Se-DEC),which was then encapsulated in niosome-nanocarriers(NISM@Chi-Se-DEC).FT-IR,DLS,FESEM,and hemolysis tests were applied to confirm its characterization and physicochemical properties.Moreover,cellular uptake,cellular toxicity,apoptosis,cell cycle,and scratch repair assays were performed to evaluate its anticancer effects on cancer cells.All anticancer assessments were repeated under X-ray irradiation conditions(fractionated 2Gy).Physicochemical characteristics of niosomes containing SeNPs and ODNs showed that it is synthesized appropriately.It revealed that the anticancer effect of NISM@Chi-Se-DEC can be significantly improved in combination with X-ray irradiation treatment.It can be concluded that NISM@Chi-Se-DEC nanocarriers have the potential as a therapeutic agent for cancer treatment,particularly in combination with radiation therapy and in-vivo experiments are necessary to confirm the efficacy of this nano-drug.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
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。
基金supported by Zanjan University of Medical Sciences,Zanjan,Iran(Grant Number:A-12-1244-16&Ethical Code:IR.ZUMS.REC.1399.316).
文摘The Myc gene is the essential oncogene in triple-negative breast cancer(TNBC).This study investigates the synergistic effects of combining Myc decoy oligodeoxynucleotides-encapsulated niosomes-selenium hybrid nanocarriers with X-irradiation exposure on the MDA-MB-468 cell line.Decoy and scramble ODNs for Myc transcription factor were designed and synthesized based on promoter sequences of the Bcl2 gene.The nanocarriers were synthesized by loading Myc ODNs and selenium into chitosan(Chi-Se-DEC),which was then encapsulated in niosome-nanocarriers(NISM@Chi-Se-DEC).FT-IR,DLS,FESEM,and hemolysis tests were applied to confirm its characterization and physicochemical properties.Moreover,cellular uptake,cellular toxicity,apoptosis,cell cycle,and scratch repair assays were performed to evaluate its anticancer effects on cancer cells.All anticancer assessments were repeated under X-ray irradiation conditions(fractionated 2Gy).Physicochemical characteristics of niosomes containing SeNPs and ODNs showed that it is synthesized appropriately.It revealed that the anticancer effect of NISM@Chi-Se-DEC can be significantly improved in combination with X-ray irradiation treatment.It can be concluded that NISM@Chi-Se-DEC nanocarriers have the potential as a therapeutic agent for cancer treatment,particularly in combination with radiation therapy and in-vivo experiments are necessary to confirm the efficacy of this nano-drug.
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。
