目的探讨羟基类固醇脱氢酶样蛋白2(hydroxysteroid dehydrogenase like 2,HSDL2)在胃癌中的表达及与临床病理特征的关系。方法采用免疫组化SP两步法检测HSDL2蛋白在90例胃癌和20例正常胃组织中的表达,分析HSDL2蛋白过表达与胃癌临床病...目的探讨羟基类固醇脱氢酶样蛋白2(hydroxysteroid dehydrogenase like 2,HSDL2)在胃癌中的表达及与临床病理特征的关系。方法采用免疫组化SP两步法检测HSDL2蛋白在90例胃癌和20例正常胃组织中的表达,分析HSDL2蛋白过表达与胃癌临床病理特征的关系,并采用GEPIA数据库进行生存分析。结果HSDL2蛋白主要定位于胃癌细胞SGC-7901和AGS的细胞质中。UALCAN数据库分析结果显示:胃癌组织中HSDL2 mRNA的表达水平明显高于正常胃组织(P<0.05)。HSDL2蛋白在胃癌组织中过表达,强阳性率为58.9%(53/90),显著高于正常胃组织(5.0%,1/20)(P<0.01)。HSDL2蛋白表达与胃癌分化程度、临床分期及肿瘤直径密切相关(P均<0.05),与患者性别、年龄及淋巴结转移无明显相关性。GEPIA数据库分析结果显示,HSDL2蛋白过表达胃癌患者无瘤生存率低于HSDL2蛋白低表达患者(P<0.05)。结论HSDL2在胃癌组织中明显过表达,其表达水平与胃癌的发生、发展及不良预后密切相关,有望成为胃癌患者预后评估的重要指标。展开更多
目的探讨人类羟基类固醇脱氢酶样蛋白2(hydroxysteroid dehydrogenase like 2,HSDL2)在人头颈鳞状细胞癌(head and neck squamous cell carcinoma,HNSCC)中的表达及临床意义。方法通过UALCAN数据库分析HNSCC中HSDL2 mRNA的表达及其与临...目的探讨人类羟基类固醇脱氢酶样蛋白2(hydroxysteroid dehydrogenase like 2,HSDL2)在人头颈鳞状细胞癌(head and neck squamous cell carcinoma,HNSCC)中的表达及临床意义。方法通过UALCAN数据库分析HNSCC中HSDL2 mRNA的表达及其与临床病理学特征的关系;应用The Human Protein Atlas(HPA)数据库和免疫组化SP两步法染色检测HNSCC中HSDL2蛋白的表达,并分析其与临床病理学特征的关系;应用HPA数据库分析HSDL2 mRNA表达与HNSCC患者生存期的关系;应用STRING数据库分析HSDL2可能参与的生物学进程及蛋白互作网络。结果与癌旁正常组织相比,HNSCC组织中HSDL2 mRNA的表达水平明显降低(P<0.01)。免疫组化染色显示HSDL2蛋白主要定位于细胞质中,且在HNSCC组织中的表达明显低于癌旁正常组织(P<0.05);HSDL2低表达与临床分期(P<0.01)、淋巴结转移(P<0.05)和患者预后密切相关(P<0.05)。GO富集分析显示,HSDL2主要参与细胞的脂肪酸代谢过程。结论HSDL2低表达与HNSCC的恶性演进密切相关,提示HSDL2在HNSCC的发生、发展中发挥抑癌基因的作用,同时其表达水平对于HNSCC的早期诊断和预后评估具有一定的指导意义。展开更多
Objective:Celastrol is a pentacyclic triterpenoid extracted from the traditional Chinese medicinal herb,Tripterygium wilfordii.This study aims to provide a scientific basis for the rational development and use of cela...Objective:Celastrol is a pentacyclic triterpenoid extracted from the traditional Chinese medicinal herb,Tripterygium wilfordii.This study aims to provide a scientific basis for the rational development and use of celastrol in breast cancer.Method:A quantitative chemical biology approach was used to investigate the protein targets and molecular mechanisms of celastrol in breast cancer cells.Results:Low-concentration celastrol exerted an anti-tumor effect by directly binding to hydroxysteroid dehydrogenase-like 2(HSDL2)and inhibiting its expression.Moreover,the expression of the pro-apoptotic protein,Bcl-2-associated X(BaX),increased,the level of the anti-apoptotic protein,B-cell lymphoma-2(Bcl-2),decreased,and the rate of apoptosis increased.After the transfection of cells with si-HSDL2,the apoptosis rate was similar to that observed after the administration of celastrol.However,apoptosis was reversed by the overexpression of HSDL2.Furthermore,our mass spectrometry(MS)data indicated a relationship between HSDL2 and the mitogen-activated protein kinase(MAPK)signaling pathway.We also found that the expression of HSDL2 was directly related to the degree of extracellular signal-regulated kinase(ERK)phosphorylation.Conclusion:Celastrol may promote apoptosis by suppressing the HSDL2/MAPK/ERK signaling pathway.展开更多
文摘目的探讨羟基类固醇脱氢酶样蛋白2(hydroxysteroid dehydrogenase like 2,HSDL2)在胃癌中的表达及与临床病理特征的关系。方法采用免疫组化SP两步法检测HSDL2蛋白在90例胃癌和20例正常胃组织中的表达,分析HSDL2蛋白过表达与胃癌临床病理特征的关系,并采用GEPIA数据库进行生存分析。结果HSDL2蛋白主要定位于胃癌细胞SGC-7901和AGS的细胞质中。UALCAN数据库分析结果显示:胃癌组织中HSDL2 mRNA的表达水平明显高于正常胃组织(P<0.05)。HSDL2蛋白在胃癌组织中过表达,强阳性率为58.9%(53/90),显著高于正常胃组织(5.0%,1/20)(P<0.01)。HSDL2蛋白表达与胃癌分化程度、临床分期及肿瘤直径密切相关(P均<0.05),与患者性别、年龄及淋巴结转移无明显相关性。GEPIA数据库分析结果显示,HSDL2蛋白过表达胃癌患者无瘤生存率低于HSDL2蛋白低表达患者(P<0.05)。结论HSDL2在胃癌组织中明显过表达,其表达水平与胃癌的发生、发展及不良预后密切相关,有望成为胃癌患者预后评估的重要指标。
文摘目的探讨人类羟基类固醇脱氢酶样蛋白2(hydroxysteroid dehydrogenase like 2,HSDL2)在人头颈鳞状细胞癌(head and neck squamous cell carcinoma,HNSCC)中的表达及临床意义。方法通过UALCAN数据库分析HNSCC中HSDL2 mRNA的表达及其与临床病理学特征的关系;应用The Human Protein Atlas(HPA)数据库和免疫组化SP两步法染色检测HNSCC中HSDL2蛋白的表达,并分析其与临床病理学特征的关系;应用HPA数据库分析HSDL2 mRNA表达与HNSCC患者生存期的关系;应用STRING数据库分析HSDL2可能参与的生物学进程及蛋白互作网络。结果与癌旁正常组织相比,HNSCC组织中HSDL2 mRNA的表达水平明显降低(P<0.01)。免疫组化染色显示HSDL2蛋白主要定位于细胞质中,且在HNSCC组织中的表达明显低于癌旁正常组织(P<0.05);HSDL2低表达与临床分期(P<0.01)、淋巴结转移(P<0.05)和患者预后密切相关(P<0.05)。GO富集分析显示,HSDL2主要参与细胞的脂肪酸代谢过程。结论HSDL2低表达与HNSCC的恶性演进密切相关,提示HSDL2在HNSCC的发生、发展中发挥抑癌基因的作用,同时其表达水平对于HNSCC的早期诊断和预后评估具有一定的指导意义。
基金the National Key Research and Development Program of China(2020YFA0908000,2022YFC2303600)the National Natural Science Foundation of China(81903866,82274182)and the Central Public Welfare Research Institutes(ZZ13-YQ-105,ZZ15-YQ-065,ZZ14-YQ-058).
文摘Objective:Celastrol is a pentacyclic triterpenoid extracted from the traditional Chinese medicinal herb,Tripterygium wilfordii.This study aims to provide a scientific basis for the rational development and use of celastrol in breast cancer.Method:A quantitative chemical biology approach was used to investigate the protein targets and molecular mechanisms of celastrol in breast cancer cells.Results:Low-concentration celastrol exerted an anti-tumor effect by directly binding to hydroxysteroid dehydrogenase-like 2(HSDL2)and inhibiting its expression.Moreover,the expression of the pro-apoptotic protein,Bcl-2-associated X(BaX),increased,the level of the anti-apoptotic protein,B-cell lymphoma-2(Bcl-2),decreased,and the rate of apoptosis increased.After the transfection of cells with si-HSDL2,the apoptosis rate was similar to that observed after the administration of celastrol.However,apoptosis was reversed by the overexpression of HSDL2.Furthermore,our mass spectrometry(MS)data indicated a relationship between HSDL2 and the mitogen-activated protein kinase(MAPK)signaling pathway.We also found that the expression of HSDL2 was directly related to the degree of extracellular signal-regulated kinase(ERK)phosphorylation.Conclusion:Celastrol may promote apoptosis by suppressing the HSDL2/MAPK/ERK signaling pathway.
