Interleukin-7 （IL-7） is an essential cytokine for the development and homeostatic maintenance of T and B lymphocytes. Binding of IL-7 to its cognate receptor, the IL-7 receptor （IL-7R）, activates multiple pathways...Interleukin-7 （IL-7） is an essential cytokine for the development and homeostatic maintenance of T and B lymphocytes. Binding of IL-7 to its cognate receptor, the IL-7 receptor （IL-7R）, activates multiple pathways that regulate lymphocyte survival, glucose uptake, proliferation and differentiation. There has been much interest in understanding how IL-7 receptor signaling is modulated at multiple interconnected network levels. This review examines how the strength of the signal through the IL-7 receptor is modulated in T and B cells, including the use of shared receptor components, signaling crosstalk, shared interaction domains, feedback loops, integrated gene regulation, multimerization and ligand competition. We discuss how these network control mechanisms could integrate to govern the properties of IL-7R signaling in lymphocytes in health and disease. Analysis of IL-7 receptor signaling at a network level in a systematic manner will allow for a comprehensive approach to understanding the impact of multiple signaling pathways on lymphocyte biology. Cellular ＆ Molecular Immunology.展开更多
The m^6A modification has been implicated as an important epitranscriptomic marker, which plays extensive roles in the regulation of transcript stability, splicing, translation, and localization. Nevertheless, only so...The m^6A modification has been implicated as an important epitranscriptomic marker, which plays extensive roles in the regulation of transcript stability, splicing, translation, and localization. Nevertheless, only some genes are repeatedly modified across various conditions and the principle of m^6A regulation remains elusive. In this study, we performed a systems-level analysis of human genes frequently regulated by m^6A modification （m^6Afreq genes） and those occasionally regulated by m^6A modification （m^6Aocca genes）. Compared to the m^6Aocca genes, the m^6Afreq genes exhibit gene importance-related features, such as lower dN/dS ratio, higher protein-protein interaction network degree, and reduced tissue expression specificity. Signaling network analysis indicates that the m^6Afreq genes are associated with downstream components of signaling cascades, high-linked signaling adaptors, and specific network motifs like incoherent feed forward loops. Moreover, functional enrichment analysis indicates significant overlaps between the m^6Afreq genes and genes involved in various layers of gene expression, such as being the microRNA targets and the regulators of RNA processing. Therefore, our findings suggest the potential interplay between m^6A epitranscriptomic regulation and other gene expression regulatory machineries.展开更多
目的探讨绿茶提取物(green tea extract,GTE)对不同的人口腔鳞癌细胞株的抗肿瘤效应及其相关机制。方法体外培养人舌鳞癌CAL-27细胞株、人舌鳞癌SCC-25细胞株、人口腔上皮癌KB细胞株,应用MTT法检测GTE对细胞增殖的影响,筛选出敏感细胞株...目的探讨绿茶提取物(green tea extract,GTE)对不同的人口腔鳞癌细胞株的抗肿瘤效应及其相关机制。方法体外培养人舌鳞癌CAL-27细胞株、人舌鳞癌SCC-25细胞株、人口腔上皮癌KB细胞株,应用MTT法检测GTE对细胞增殖的影响,筛选出敏感细胞株,用流式细胞术检测GTE对CAL-27细胞周期的影响,采用蛋白芯片技术检测GTE对CAL-27细胞株蛋白表达的影响,并应用Western blot检测周期蛋白依赖性激酶4(cyclin-dependent kinases,CDK4)、周期蛋白依赖性激酶6(cyclin-dependent kinases,CDK6)、磷酸化3-磷酸肌醇依赖性蛋白激酶-1(phospho-3-phosphoinositide-dependent protein kinase-1,p-PDK1)蛋白表达情况。结果与对照组比较,50、100、200、400μg/m L GTE作用于CAL-27细胞抑制率升高,100、200、400μg/m L GTE作用于KB细胞抑制率升高,25、50、100、200、400μg/m L GTE作用于SCC-25细胞抑制率亦升高,差异均有统计学意义(P<0.01),并呈剂量依赖性。流式细胞术显示:与对照组比较,50μg/m L GTE介导CAL-27细胞G2/M期阻滞(P<0.05);100μg/m L GTE能够介导CAL-27细胞S期及G2/M期阻滞(P<0.01),G0/G1期细胞减少(P<0.01)。应用蛋白芯片技术共分析107种蛋白,应用GTE处理后,CAL-27细胞共有13种蛋白发生明显变化。应用Western blot技术确认了25、50、100μg/m L GTE作用于CAL-27细胞后p-PDK1、CDK4、CDK6蛋白表达,药物浓度越高,抑制率越高,差异有统计学意义(P<0.05)。结论 GTE能够抑制多种类型人口腔鳞癌细胞株的增殖,敏感细胞株为CAL-27。GTE主要影响表皮生长因子受体(EGFR)和Notch信号传导通路,并通过以上信号传导通路影响细胞周期相关蛋白表达水平的变化,导致细胞周期S期及G2/M期阻滞。展开更多
文摘Interleukin-7 （IL-7） is an essential cytokine for the development and homeostatic maintenance of T and B lymphocytes. Binding of IL-7 to its cognate receptor, the IL-7 receptor （IL-7R）, activates multiple pathways that regulate lymphocyte survival, glucose uptake, proliferation and differentiation. There has been much interest in understanding how IL-7 receptor signaling is modulated at multiple interconnected network levels. This review examines how the strength of the signal through the IL-7 receptor is modulated in T and B cells, including the use of shared receptor components, signaling crosstalk, shared interaction domains, feedback loops, integrated gene regulation, multimerization and ligand competition. We discuss how these network control mechanisms could integrate to govern the properties of IL-7R signaling in lymphocytes in health and disease. Analysis of IL-7 receptor signaling at a network level in a systematic manner will allow for a comprehensive approach to understanding the impact of multiple signaling pathways on lymphocyte biology. Cellular ＆ Molecular Immunology.
基金supported by the National Natural Science Foundation of China (Grant Nos. 81670462 and 81422006 to QC)China Postdoctoral Science Foundation (Grant No. 2016M591024 to YZ)
文摘The m^6A modification has been implicated as an important epitranscriptomic marker, which plays extensive roles in the regulation of transcript stability, splicing, translation, and localization. Nevertheless, only some genes are repeatedly modified across various conditions and the principle of m^6A regulation remains elusive. In this study, we performed a systems-level analysis of human genes frequently regulated by m^6A modification （m^6Afreq genes） and those occasionally regulated by m^6A modification （m^6Aocca genes）. Compared to the m^6Aocca genes, the m^6Afreq genes exhibit gene importance-related features, such as lower dN/dS ratio, higher protein-protein interaction network degree, and reduced tissue expression specificity. Signaling network analysis indicates that the m^6Afreq genes are associated with downstream components of signaling cascades, high-linked signaling adaptors, and specific network motifs like incoherent feed forward loops. Moreover, functional enrichment analysis indicates significant overlaps between the m^6Afreq genes and genes involved in various layers of gene expression, such as being the microRNA targets and the regulators of RNA processing. Therefore, our findings suggest the potential interplay between m^6A epitranscriptomic regulation and other gene expression regulatory machineries.
文摘目的探讨绿茶提取物(green tea extract,GTE)对不同的人口腔鳞癌细胞株的抗肿瘤效应及其相关机制。方法体外培养人舌鳞癌CAL-27细胞株、人舌鳞癌SCC-25细胞株、人口腔上皮癌KB细胞株,应用MTT法检测GTE对细胞增殖的影响,筛选出敏感细胞株,用流式细胞术检测GTE对CAL-27细胞周期的影响,采用蛋白芯片技术检测GTE对CAL-27细胞株蛋白表达的影响,并应用Western blot检测周期蛋白依赖性激酶4(cyclin-dependent kinases,CDK4)、周期蛋白依赖性激酶6(cyclin-dependent kinases,CDK6)、磷酸化3-磷酸肌醇依赖性蛋白激酶-1(phospho-3-phosphoinositide-dependent protein kinase-1,p-PDK1)蛋白表达情况。结果与对照组比较,50、100、200、400μg/m L GTE作用于CAL-27细胞抑制率升高,100、200、400μg/m L GTE作用于KB细胞抑制率升高,25、50、100、200、400μg/m L GTE作用于SCC-25细胞抑制率亦升高,差异均有统计学意义(P<0.01),并呈剂量依赖性。流式细胞术显示:与对照组比较,50μg/m L GTE介导CAL-27细胞G2/M期阻滞(P<0.05);100μg/m L GTE能够介导CAL-27细胞S期及G2/M期阻滞(P<0.01),G0/G1期细胞减少(P<0.01)。应用蛋白芯片技术共分析107种蛋白,应用GTE处理后,CAL-27细胞共有13种蛋白发生明显变化。应用Western blot技术确认了25、50、100μg/m L GTE作用于CAL-27细胞后p-PDK1、CDK4、CDK6蛋白表达,药物浓度越高,抑制率越高,差异有统计学意义(P<0.05)。结论 GTE能够抑制多种类型人口腔鳞癌细胞株的增殖,敏感细胞株为CAL-27。GTE主要影响表皮生长因子受体(EGFR)和Notch信号传导通路,并通过以上信号传导通路影响细胞周期相关蛋白表达水平的变化,导致细胞周期S期及G2/M期阻滞。
