目的:探究S100钙结合蛋白A4 (S100 Calcium Binding Protein A4, S100A4)在银屑病炎症中的作用机制。方法:在HaCat细胞中使用S100A4的抗体进行改进的紫外交联免疫共沉淀结合高通量测序(improved RNA Binding Protein Immunoprecipitatio...目的:探究S100钙结合蛋白A4 (S100 Calcium Binding Protein A4, S100A4)在银屑病炎症中的作用机制。方法:在HaCat细胞中使用S100A4的抗体进行改进的紫外交联免疫共沉淀结合高通量测序(improved RNA Binding Protein Immunoprecipitation high throughput sequencing, iRIP-seq)技术获得与S100A4互作的RNA,将相关基因序列比对KEGG数据库来明确S100A4调控的炎症通路。结果:S100A4结合的靶RNA所在基因与MAPK信号通路、核糖体、内质网中的蛋白质加工、糖尿病并发症中的AGE-RAGE信号通路、膀胱癌、慢性髓样白血病、弓形体病、结肠直肠癌、破骨细胞分化、军团杆菌病等功能通路的调节有关,表明S100A4可能是调节银屑病及其并发症的一种关键炎症介质。结论:S100A4在银屑病炎症机制中具有潜在的调控作用,这些发现为S100A4作为银屑病发病炎症介质提供了新的证据。展开更多
目的:研究S100A4核定位在胰腺癌(pancreatic cancer,PC)转移中的作用与机制。方法:利用PC病程进展的组织芯片,通过免疫组化和HALO数字病理精准分析平台等技术,定量S100A4在组织细胞,特别是胞核中的表达情况,统计分析各检测指标与临床参...目的:研究S100A4核定位在胰腺癌(pancreatic cancer,PC)转移中的作用与机制。方法:利用PC病程进展的组织芯片,通过免疫组化和HALO数字病理精准分析平台等技术,定量S100A4在组织细胞,特别是胞核中的表达情况,统计分析各检测指标与临床参数及生存期之间的关系。通过分子结构信息学分析、质粒构建与转染以构建基因调控的不同分组细胞研究模型;利用核质蛋白分离、免疫共沉淀、Western blot、划痕实验、Transwell实验、靶向剪切及转座酶技术(cleavage under targets and tagmentation,CUT&Tag)等研究S100A4核定位在PC转移中的作用与机制。结果:S100A4的高表达及其核定位与PC的T、N分期和不良预后正相关。PC细胞中S100A4核定位受小泛素相关修饰物(small ubiquitin-related modifier,SUMO)修饰调控,泛素结合酶9介导了PC细胞中S100A4的K22和K96位点与SUMO1结合,并通过SUMO特异性蛋白酶1实现去SUMO化,动态平衡PC细胞中S100A4的SUMO化修饰水平;调控S100A4蛋白的SUMO化修饰可改变PC细胞的体外转移能力;CUT&Tag测序结果证明S100A4核定位参与调控与肿瘤转移功能相关的基因网络。结论:S100A4核定位可提示PC预后不良,有望成为临床治疗方案制定的重要依据。发现阻断或抑制S100A4核定位的办法,可能成为抑制PC转移,特别是早期转移,改善PC患者预后的新靶点。展开更多
Background:S100A8 is a member of the S100 protein family and plays a pivotal role in regulating inflammation and tumor progression.This study aimed to comprehensively assess the expression patterns and functional role...Background:S100A8 is a member of the S100 protein family and plays a pivotal role in regulating inflammation and tumor progression.This study aimed to comprehensively assess the expression patterns and functional roles of S100A8 in glioma progression.Methods:Glioma tissues were collected from 98 patients who underwent surgical treatment at Fudan University Shanghai Cancer Center.S100A8 expression in glioma tissues was analyzed using immunohistochemistry(IHC)to establish its correlation with clinicopathological features in patients.The expression and prognostic effect of S100A8 in glioma were analyzed using TCGA and CGGA public databases.Then,we investigated the role of S100A8 in glioma through a series of in vivo and in vitro experiments including Transwell,wound healing,CCK8,and intracranial tumor models.Subsequently,bioinformatics analysis,single-cell sequencing and coimmunopre-cipitation(Co-IP)were used to explore the underlying mechanism.Results:S100A8 was upregulated in gliomas compared to paracancerous tissues,and this phenotype was sig-nificantly correlated with poor prognosis.Subgroup analysis showed that S100A8 expression was higher in the high-grade glioma(HGG)group than that in the low-grade glioma(LGG)group.S100A8 overexpression in glioma cell lines promoted cell proliferation,migration and invasion,while silencing S100A8 reversed these effects.In vivo experiments showed that S100A8 knockdown can significantly reduce the tumor burden of glioma cells.Notably,S100A8 was observed to stimulate microglial M2 polarization by interacting with TLR4,which subse-quently induced NF-𝜅B signaling and IL-10 secretion within the tumor microenvironment.Conclusions:S100A8 promotes tumor progression by inducing phenotypic polarization of microglia through the TLR4/IL-10 signaling pathway in glioma.It might represent a therapeutic target for further basic research or clinical management of glioma.展开更多
文摘目的:探究S100钙结合蛋白A4 (S100 Calcium Binding Protein A4, S100A4)在银屑病炎症中的作用机制。方法:在HaCat细胞中使用S100A4的抗体进行改进的紫外交联免疫共沉淀结合高通量测序(improved RNA Binding Protein Immunoprecipitation high throughput sequencing, iRIP-seq)技术获得与S100A4互作的RNA,将相关基因序列比对KEGG数据库来明确S100A4调控的炎症通路。结果:S100A4结合的靶RNA所在基因与MAPK信号通路、核糖体、内质网中的蛋白质加工、糖尿病并发症中的AGE-RAGE信号通路、膀胱癌、慢性髓样白血病、弓形体病、结肠直肠癌、破骨细胞分化、军团杆菌病等功能通路的调节有关,表明S100A4可能是调节银屑病及其并发症的一种关键炎症介质。结论:S100A4在银屑病炎症机制中具有潜在的调控作用,这些发现为S100A4作为银屑病发病炎症介质提供了新的证据。
文摘目的:研究S100A4核定位在胰腺癌(pancreatic cancer,PC)转移中的作用与机制。方法:利用PC病程进展的组织芯片,通过免疫组化和HALO数字病理精准分析平台等技术,定量S100A4在组织细胞,特别是胞核中的表达情况,统计分析各检测指标与临床参数及生存期之间的关系。通过分子结构信息学分析、质粒构建与转染以构建基因调控的不同分组细胞研究模型;利用核质蛋白分离、免疫共沉淀、Western blot、划痕实验、Transwell实验、靶向剪切及转座酶技术(cleavage under targets and tagmentation,CUT&Tag)等研究S100A4核定位在PC转移中的作用与机制。结果:S100A4的高表达及其核定位与PC的T、N分期和不良预后正相关。PC细胞中S100A4核定位受小泛素相关修饰物(small ubiquitin-related modifier,SUMO)修饰调控,泛素结合酶9介导了PC细胞中S100A4的K22和K96位点与SUMO1结合,并通过SUMO特异性蛋白酶1实现去SUMO化,动态平衡PC细胞中S100A4的SUMO化修饰水平;调控S100A4蛋白的SUMO化修饰可改变PC细胞的体外转移能力;CUT&Tag测序结果证明S100A4核定位参与调控与肿瘤转移功能相关的基因网络。结论:S100A4核定位可提示PC预后不良,有望成为临床治疗方案制定的重要依据。发现阻断或抑制S100A4核定位的办法,可能成为抑制PC转移,特别是早期转移,改善PC患者预后的新靶点。
基金supported by the National Natural Science Foundation of China(grant numbers:82103429 and 82173177).
文摘Background:S100A8 is a member of the S100 protein family and plays a pivotal role in regulating inflammation and tumor progression.This study aimed to comprehensively assess the expression patterns and functional roles of S100A8 in glioma progression.Methods:Glioma tissues were collected from 98 patients who underwent surgical treatment at Fudan University Shanghai Cancer Center.S100A8 expression in glioma tissues was analyzed using immunohistochemistry(IHC)to establish its correlation with clinicopathological features in patients.The expression and prognostic effect of S100A8 in glioma were analyzed using TCGA and CGGA public databases.Then,we investigated the role of S100A8 in glioma through a series of in vivo and in vitro experiments including Transwell,wound healing,CCK8,and intracranial tumor models.Subsequently,bioinformatics analysis,single-cell sequencing and coimmunopre-cipitation(Co-IP)were used to explore the underlying mechanism.Results:S100A8 was upregulated in gliomas compared to paracancerous tissues,and this phenotype was sig-nificantly correlated with poor prognosis.Subgroup analysis showed that S100A8 expression was higher in the high-grade glioma(HGG)group than that in the low-grade glioma(LGG)group.S100A8 overexpression in glioma cell lines promoted cell proliferation,migration and invasion,while silencing S100A8 reversed these effects.In vivo experiments showed that S100A8 knockdown can significantly reduce the tumor burden of glioma cells.Notably,S100A8 was observed to stimulate microglial M2 polarization by interacting with TLR4,which subse-quently induced NF-𝜅B signaling and IL-10 secretion within the tumor microenvironment.Conclusions:S100A8 promotes tumor progression by inducing phenotypic polarization of microglia through the TLR4/IL-10 signaling pathway in glioma.It might represent a therapeutic target for further basic research or clinical management of glioma.
