目的:研究Ras及Rab作用因子1(Ras and Rab interactor 1,RIN1)、SIAH2在胃癌组织表达及其与临床病理因素的关系.方法:用免疫组织化学方法检测R I N1和S I A H2在80例胃癌及40例正常胃组织中的表达及相关性.结果:RIN1和SIAH2蛋白阳性表...目的:研究Ras及Rab作用因子1(Ras and Rab interactor 1,RIN1)、SIAH2在胃癌组织表达及其与临床病理因素的关系.方法:用免疫组织化学方法检测R I N1和S I A H2在80例胃癌及40例正常胃组织中的表达及相关性.结果:RIN1和SIAH2蛋白阳性表达率胃癌中分别为61.2%和60.0%,正常胃组织中分别为32.5%和27.5%,胃癌组织与正常胃组织比较R I N1和S I A H2蛋白阳性表达率的差异有统计学意义(P<0.05),胃癌中,RIN1表达与肿瘤大小、临床分期、组织学分级、浆膜浸润及淋巴结转移有关(P<0.05),与性别、年龄无关(P>0.05),而SIAH2表达与组织学分化程度、临床分期、淋巴结转移及浆膜浸润有关(P<0.05),与肿瘤大小无关(P>0.05),RIN1和SIAH2在胃癌组织中的表达呈正相关(r=0.607,P<0.01).结论:RIN1、SIAH2过表达在胃癌组织的发展及浸润转移中具有重要的作用,二者的表达可能与胃癌的不良预后有密切关系,他们有望成为胃癌的早期诊断指标和治疗靶点.展开更多
Purpose:Approximately 1/3 of brain tumors are gliomas.Previous glioma-related studies have reported increased expression of periostin(POSTN)in these cancerous tissues,but the role and mechanism of POSTN in glioma deve...Purpose:Approximately 1/3 of brain tumors are gliomas.Previous glioma-related studies have reported increased expression of periostin(POSTN)in these cancerous tissues,but the role and mechanism of POSTN in glioma development remain unclear.Methods:Nanoscale liquid chromatography coupled with tandem mass spectrometry(nano LC-MS/MS)and RNA sequencing were used to identify diferential protein and mRNA expression in clinical glioma samples.Quantitative real-time PCR(qRT-PCR)was used to measure the expression of POSTN in tissues and cells.The efects of POSTN on glioma cell migration and invasion were examined using wound healing,Transwell,and three-dimensional spheroid assays in vitro and a nude mouse xenograft model in vivo.The efects of POSTN on the stability,endocytosis,and degradation of EGFR were examined by immunoblotting and immunofuorescence staining.Truncation mutation analysis was performed to investigate direct interactions between POSTN and EGFR.Immunohistochemical staining was carried out to confrm the clinical signifcance of POSTN.Results:Overexpression of POSTN induced epithelial-to-mesenchymal transition(EMT)in glioma cells in vivo and in vitro.Mechanistically,POSTN downregulation inhibited EGFR signaling by promoting EGFR endocytosis and degradation.In addition,POSTN was found to bind to EGFR and RIN1,inhibiting EGFR endocytosis and degradation and thus activating the PI3K-Akt signaling pathway.Conclusion:These fndings indicate the mechanism by which the POSTN/EGFR/RIN1 axis inhibits EGFR endocytosis and degradation,resulting in glioma cell EMT through the PI3K-AKT signaling pathway.Targeting POSTN/EGFR/RIN1 interactions may guarantee benefcial outcomes of glioma treatment.展开更多
文摘目的:研究Ras及Rab作用因子1(Ras and Rab interactor 1,RIN1)、SIAH2在胃癌组织表达及其与临床病理因素的关系.方法:用免疫组织化学方法检测R I N1和S I A H2在80例胃癌及40例正常胃组织中的表达及相关性.结果:RIN1和SIAH2蛋白阳性表达率胃癌中分别为61.2%和60.0%,正常胃组织中分别为32.5%和27.5%,胃癌组织与正常胃组织比较R I N1和S I A H2蛋白阳性表达率的差异有统计学意义(P<0.05),胃癌中,RIN1表达与肿瘤大小、临床分期、组织学分级、浆膜浸润及淋巴结转移有关(P<0.05),与性别、年龄无关(P>0.05),而SIAH2表达与组织学分化程度、临床分期、淋巴结转移及浆膜浸润有关(P<0.05),与肿瘤大小无关(P>0.05),RIN1和SIAH2在胃癌组织中的表达呈正相关(r=0.607,P<0.01).结论:RIN1、SIAH2过表达在胃癌组织的发展及浸润转移中具有重要的作用,二者的表达可能与胃癌的不良预后有密切关系,他们有望成为胃癌的早期诊断指标和治疗靶点.
基金supported by grants from National Natural Science Foundation of China (81772682)the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).
文摘Purpose:Approximately 1/3 of brain tumors are gliomas.Previous glioma-related studies have reported increased expression of periostin(POSTN)in these cancerous tissues,but the role and mechanism of POSTN in glioma development remain unclear.Methods:Nanoscale liquid chromatography coupled with tandem mass spectrometry(nano LC-MS/MS)and RNA sequencing were used to identify diferential protein and mRNA expression in clinical glioma samples.Quantitative real-time PCR(qRT-PCR)was used to measure the expression of POSTN in tissues and cells.The efects of POSTN on glioma cell migration and invasion were examined using wound healing,Transwell,and three-dimensional spheroid assays in vitro and a nude mouse xenograft model in vivo.The efects of POSTN on the stability,endocytosis,and degradation of EGFR were examined by immunoblotting and immunofuorescence staining.Truncation mutation analysis was performed to investigate direct interactions between POSTN and EGFR.Immunohistochemical staining was carried out to confrm the clinical signifcance of POSTN.Results:Overexpression of POSTN induced epithelial-to-mesenchymal transition(EMT)in glioma cells in vivo and in vitro.Mechanistically,POSTN downregulation inhibited EGFR signaling by promoting EGFR endocytosis and degradation.In addition,POSTN was found to bind to EGFR and RIN1,inhibiting EGFR endocytosis and degradation and thus activating the PI3K-Akt signaling pathway.Conclusion:These fndings indicate the mechanism by which the POSTN/EGFR/RIN1 axis inhibits EGFR endocytosis and degradation,resulting in glioma cell EMT through the PI3K-AKT signaling pathway.Targeting POSTN/EGFR/RIN1 interactions may guarantee benefcial outcomes of glioma treatment.
