目的·检测Fas相关死亡结构域蛋白(Fas-associated protein with death domain,FADD)在头颈部鳞状细胞癌(head and neck squamous cell carcinoma,HNSCC)中的表达水平,并探究FADD促进HNSCC细胞增殖的分子机制。方法·利用GEPIA ...目的·检测Fas相关死亡结构域蛋白(Fas-associated protein with death domain,FADD)在头颈部鳞状细胞癌(head and neck squamous cell carcinoma,HNSCC)中的表达水平,并探究FADD促进HNSCC细胞增殖的分子机制。方法·利用GEPIA 2数据库分析肿瘤组织中FADD表达水平及其与预后的关系;通过对HNSCC组织进行免疫组织化学染色(immunohistochemistry staining,IHC),探究FADD在正常、不典型增生和肿瘤组织中的表达水平变化;构建稳定低表达FADD的人HNSCC Fadu、HSC3细胞株,并通过蛋白印迹实验和实时荧光定量PCR(quantitative real-time PCR,qRT-PCR)方法进行验证;使用LiveCyte活细胞追踪系统、克隆形成、细胞活力检测等方法探究FADD对HNSCC细胞增殖水平的调控作用;使用免疫共沉淀串联质谱(co-immunoprecipitation mass spectrum,Co-IP/MS)鉴定与FADD发生相互作用的蛋白,并应用CRISPR/Cas9技术、LiveCyte活细胞追踪系统、蛋白印迹实验等方法对与FADD相互作用的蛋白进行进一步机制研究。结果·数据库分析显示FADD在头颈鳞癌中显著高表达,并与患者不良预后相关。免疫组化染色表明FADD在HNSCC患者正常组织、不典型增生及肿瘤组织中的表达水平呈现递增趋势。在HNSCC细胞中敲低FADD后,与对照组相比,细胞的增殖能力显著降低,形成克隆数减少。Co-IP/MS结果显示,FADD与CUT样同源盒1(CUT-like homeobox 1,CUX1)蛋白存在相互作用,敲低FADD后CUX1表达水平升高。同时,在HNSCC细胞中敲除CUX1能够显著促进肿瘤细胞增殖能力。敲除CUX1可部分逆转FADD低表达引起的增殖抑制。结论·FADD在HNSCC中具有显著促癌作用,并与不良预后相关。FADD可通过与CUX1发生相互作用降低其表达水平进一步调控肿瘤细胞的增殖能力。展开更多
Cux（Cu2O）1-x（0.09 x 1.00） granular films with thickness about 280 nm have been fabricated by direct current reactive magnetron sputtering. The atomic ratio x can be controlled by the oxygen flow rate during Cux（C...Cux（Cu2O）1-x（0.09 x 1.00） granular films with thickness about 280 nm have been fabricated by direct current reactive magnetron sputtering. The atomic ratio x can be controlled by the oxygen flow rate during Cux（Cu2O）1-x deposition. Room-temperature ferromagnetism（FM） is found in all of the samples. The saturated magnetization increases at first and then decreases with the decrease of x. The photoluminescence spectra show that the magnetization is closely correlated with the Cu vacancies in the Cux（Cu2O）1-x granular films. Fundamentally, the FM could be understood by the Stoner model based on the charge transfer mechanism. These results may provide solid evidence and physical insights on the origin of FM in the Cu2O-based oxides diluted magnetic semiconductors, especially for systems without intentional magnetic atom doping.展开更多
文摘目的·检测Fas相关死亡结构域蛋白(Fas-associated protein with death domain,FADD)在头颈部鳞状细胞癌(head and neck squamous cell carcinoma,HNSCC)中的表达水平,并探究FADD促进HNSCC细胞增殖的分子机制。方法·利用GEPIA 2数据库分析肿瘤组织中FADD表达水平及其与预后的关系;通过对HNSCC组织进行免疫组织化学染色(immunohistochemistry staining,IHC),探究FADD在正常、不典型增生和肿瘤组织中的表达水平变化;构建稳定低表达FADD的人HNSCC Fadu、HSC3细胞株,并通过蛋白印迹实验和实时荧光定量PCR(quantitative real-time PCR,qRT-PCR)方法进行验证;使用LiveCyte活细胞追踪系统、克隆形成、细胞活力检测等方法探究FADD对HNSCC细胞增殖水平的调控作用;使用免疫共沉淀串联质谱(co-immunoprecipitation mass spectrum,Co-IP/MS)鉴定与FADD发生相互作用的蛋白,并应用CRISPR/Cas9技术、LiveCyte活细胞追踪系统、蛋白印迹实验等方法对与FADD相互作用的蛋白进行进一步机制研究。结果·数据库分析显示FADD在头颈鳞癌中显著高表达,并与患者不良预后相关。免疫组化染色表明FADD在HNSCC患者正常组织、不典型增生及肿瘤组织中的表达水平呈现递增趋势。在HNSCC细胞中敲低FADD后,与对照组相比,细胞的增殖能力显著降低,形成克隆数减少。Co-IP/MS结果显示,FADD与CUT样同源盒1(CUT-like homeobox 1,CUX1)蛋白存在相互作用,敲低FADD后CUX1表达水平升高。同时,在HNSCC细胞中敲除CUX1能够显著促进肿瘤细胞增殖能力。敲除CUX1可部分逆转FADD低表达引起的增殖抑制。结论·FADD在HNSCC中具有显著促癌作用,并与不良预后相关。FADD可通过与CUX1发生相互作用降低其表达水平进一步调控肿瘤细胞的增殖能力。
基金Project supported by the National Natural Science Foundation of China(Grant Nos.11104148,51101088,and 51171082)the Tianjin Natural Science Foundation,China(Grant Nos.14JCZDJC37700 and 13JCQNJC02800)+1 种基金the Specialized Research Fund for the Doctoral Program of Higher Education,China(Grant No.20110031110034)the Fundamental Research Funds for the Central Universities,China
文摘Cux（Cu2O）1-x（0.09 x 1.00） granular films with thickness about 280 nm have been fabricated by direct current reactive magnetron sputtering. The atomic ratio x can be controlled by the oxygen flow rate during Cux（Cu2O）1-x deposition. Room-temperature ferromagnetism（FM） is found in all of the samples. The saturated magnetization increases at first and then decreases with the decrease of x. The photoluminescence spectra show that the magnetization is closely correlated with the Cu vacancies in the Cux（Cu2O）1-x granular films. Fundamentally, the FM could be understood by the Stoner model based on the charge transfer mechanism. These results may provide solid evidence and physical insights on the origin of FM in the Cu2O-based oxides diluted magnetic semiconductors, especially for systems without intentional magnetic atom doping.
