目的:探讨泛素特异性蛋白酶18(ubiquitin specific peptidase 18,USP18)在宫颈鳞状细胞癌组织中的表达及意义,分析USP18的表达水平与宫颈癌临床病例特征的关系。方法:实时荧光定量PCR法检测USP18在30例新鲜宫颈癌组织及癌旁宫颈组织中m...目的:探讨泛素特异性蛋白酶18(ubiquitin specific peptidase 18,USP18)在宫颈鳞状细胞癌组织中的表达及意义,分析USP18的表达水平与宫颈癌临床病例特征的关系。方法:实时荧光定量PCR法检测USP18在30例新鲜宫颈癌组织及癌旁宫颈组织中mRNA的表达情况,蛋白免疫印迹法检测USP18在6例新鲜宫颈癌组织及癌旁宫颈组织中蛋白的表达情况,免疫组织化学染色方法检测USP18在60例宫颈癌及癌旁组织石蜡包埋标本中的蛋白表达情况,并分析USP18的表达与宫颈癌临床病理特征之间的相关性。结果:新鲜组织中,宫颈癌组织的USP18在mRNA水平和蛋白水平均显著高于癌旁宫颈组织(P<0.01,P<0.01);石蜡组织中,宫颈癌组织的USP18表达显著高于癌旁宫颈组织(86.7%vs 33.9%,P<0.01),USP18的表达与宫颈癌患者的年龄无显著相关性(P>0.05),但是与肿瘤分化程度和淋巴结转移情况有显著相关性(P<0.01)。结论:宫颈癌组织中USP18的表达显著升高,并与宫颈癌的分化转移相关,有望成为宫颈癌的一种新的分子标志物。展开更多
Ubiquitin-specific peptidase 18(USP18)plays an important role in the development of CD11b^(+)dendritic cells(DCs)and Th17 cells,however,its role in the differentiation of other T cell subsets,especially in regulatory ...Ubiquitin-specific peptidase 18(USP18)plays an important role in the development of CD11b^(+)dendritic cells(DCs)and Th17 cells,however,its role in the differentiation of other T cell subsets,especially in regulatory T(Treg)cells,is unknown.In our study,we used Usp18 K0 mice to study the loss of USP18 on the impact of Treg cell differentiation and function.We found that USP18 deficiency upregulates the differentiation of Treg cells,which may lead to disrupted homeostasis of peripheral T cells,and downregulates INF-y,IL-2,IL-17A producing CD4^(+)T cells and INF-γproducing CD8^(+)T cells.Mechanistically,we also found that the upre-gulation of Tregs is due to elevated expression of CD25 in Usp18 KO mice.Finally,we found that the suppressive function of Usp18 KO Tregs is downregulated.Altogether,our study was the first to identify the role of USP18 in Tregs differentiation and its suppressive function,which may provide a new reference for the treatment of Treg function in many autoimmune diseases,and USP18 can be used as a new therapeutic target for precise medical treatment.展开更多
文摘目的:探讨泛素特异性蛋白酶18(ubiquitin specific peptidase 18,USP18)在宫颈鳞状细胞癌组织中的表达及意义,分析USP18的表达水平与宫颈癌临床病例特征的关系。方法:实时荧光定量PCR法检测USP18在30例新鲜宫颈癌组织及癌旁宫颈组织中mRNA的表达情况,蛋白免疫印迹法检测USP18在6例新鲜宫颈癌组织及癌旁宫颈组织中蛋白的表达情况,免疫组织化学染色方法检测USP18在60例宫颈癌及癌旁组织石蜡包埋标本中的蛋白表达情况,并分析USP18的表达与宫颈癌临床病理特征之间的相关性。结果:新鲜组织中,宫颈癌组织的USP18在mRNA水平和蛋白水平均显著高于癌旁宫颈组织(P<0.01,P<0.01);石蜡组织中,宫颈癌组织的USP18表达显著高于癌旁宫颈组织(86.7%vs 33.9%,P<0.01),USP18的表达与宫颈癌患者的年龄无显著相关性(P>0.05),但是与肿瘤分化程度和淋巴结转移情况有显著相关性(P<0.01)。结论:宫颈癌组织中USP18的表达显著升高,并与宫颈癌的分化转移相关,有望成为宫颈癌的一种新的分子标志物。
基金supported by National NaturalScience Foundation of China(grant numbers 81861138002,81722002,31970839,31900654)。
文摘Ubiquitin-specific peptidase 18(USP18)plays an important role in the development of CD11b^(+)dendritic cells(DCs)and Th17 cells,however,its role in the differentiation of other T cell subsets,especially in regulatory T(Treg)cells,is unknown.In our study,we used Usp18 K0 mice to study the loss of USP18 on the impact of Treg cell differentiation and function.We found that USP18 deficiency upregulates the differentiation of Treg cells,which may lead to disrupted homeostasis of peripheral T cells,and downregulates INF-y,IL-2,IL-17A producing CD4^(+)T cells and INF-γproducing CD8^(+)T cells.Mechanistically,we also found that the upre-gulation of Tregs is due to elevated expression of CD25 in Usp18 KO mice.Finally,we found that the suppressive function of Usp18 KO Tregs is downregulated.Altogether,our study was the first to identify the role of USP18 in Tregs differentiation and its suppressive function,which may provide a new reference for the treatment of Treg function in many autoimmune diseases,and USP18 can be used as a new therapeutic target for precise medical treatment.
