目的:探讨外源性p53AIP1(p53-regulated apoptosis-inducing protein 1)基因抗肿瘤效应及其作用机制,以评估p53AIP1基因在肿瘤基因治疗中应用的可行性。方法:构建携带p53AIP1基因的重组复制缺陷型腺病毒Ad-p53AIP1,感染人肝癌细胞HepG2...目的:探讨外源性p53AIP1(p53-regulated apoptosis-inducing protein 1)基因抗肿瘤效应及其作用机制,以评估p53AIP1基因在肿瘤基因治疗中应用的可行性。方法:构建携带p53AIP1基因的重组复制缺陷型腺病毒Ad-p53AIP1,感染人肝癌细胞HepG2,应用MTT比色法、Western blotting、流式细胞术、罗丹明染色以及电镜等观察外源性p53AIP1基因表达对肿瘤细胞的作用及其相关机制。小鼠皮下接种感染Ad-p53AIP1的小鼠乳腺癌4T1细胞,观察Ad-p53AIP1对肿瘤细胞体内成瘤性的影响;建立4T1细胞皮下移植瘤小鼠模型,直接瘤内多点注射重组腺病毒,观察Ad-p53AIP1的抗肿瘤疗效。结果:感染Ad-p53AIP1的HepG2细胞能够高效表达P53AIP1蛋白。MTT检测显示Ad-p53AIP1对人肝癌细胞HepG2的生长抑制率达50%以上;流式细胞术分析证实p53AIP1使肿瘤细胞周期阻滞于G_2/M期;罗丹明染色、电镜观察以及凋亡相关蛋白PARP表达的检测均证实p53AIP1能诱导肿瘤细胞发生明显凋亡。感染Ad-p53AIP1的肿瘤细胞体内成瘤受到非常明显的抑制(P<0.01),Ad-p53AIP1瘤体注射对移植瘤生长也有明显的抑制作用(P<0.05)。Western blotting以及RT-PCR检测证实Ad-p53AIP1对p53 mRNA表达无影响,能下调mdm2基因的表达;p53AIP1能上调P53蛋白的表达、下调MDM2蛋白的表达水平,同时还影响P21等细胞周期相关蛋白和凋亡相关蛋白的表达。结论:p53AIP1有明显的体内外抗肿瘤作用,其作用机制与其反向调控P53蛋白、调控多种细胞周期和细胞凋亡相关蛋白、诱导细胞周期阻滞和细胞凋亡有关,该基因在肿瘤基因治疗中具有潜在的应用前景。展开更多
Apical actin filaments are highly dynamic structures that are crucial for rapid pollen tube growth, but the mechanisms regulating their dynamics and spatial organization remain incompletely understood. We here identif...Apical actin filaments are highly dynamic structures that are crucial for rapid pollen tube growth, but the mechanisms regulating their dynamics and spatial organization remain incompletely understood. We here identify that AtAIP1-1 is important for regulating the turnover and organization of apical actin filaments in pollen tubes. AtAIP1-1 is distributed uniformly in the pollen tube and loss of function of AtAIP1-1 affects the organization of the actin cytoskeleton in the pollen tube. Specifically, actin filaments became disorganized within the apical region of aip1-1 pollen tubes. Consistent with the role of apical actin filaments in spatially restricting vesicles in pollen tubes, the apical region occupied by vesicles becomes enlarged in aip1-1 pollen tubes compared to WT. Using ADF1 as a representative actin-depolymerizing factor, we demonstrate that AtAIP1-1 enhances ADF1-mediated actin depolymerization and filament severing in vitro, although AtAIP1-1 alone does not have an obvious effect on actin assembly and disassembly. The dynamics of apical actin filaments are reduced in aip1-1 pollen tubes compared to WT. Our study suggests that AtAIP1-1 works together with ADF to act as a module in regulating the dynamics of apical actin filaments to facilitate the construction of the unique "apical actin structure" in the pollen tube.展开更多
Background:Cancer poses a significant global challenge,and with the pro-jected rise in cancer incidence,there is an urgent need to discover new targets and treatments to improve patient outcomes.Recent advancements in...Background:Cancer poses a significant global challenge,and with the pro-jected rise in cancer incidence,there is an urgent need to discover new targets and treatments to improve patient outcomes.Recent advancements in geno-mics technologies have enhanced our understanding of cancer's complexities and led to the emergence of pan‐cancer analysis as a valuable approach for identifying tumor targets.Torsin‐1A‐interacting protein 1(TOR1AIP1)is a membrane protein involved in various cellular processes.Emerging evidence suggests its potential involvement in cancer.Methods:In this study,we conducted a comprehensive analysis of multiple databases to explore TOR1AIP1 expression across different cancer types and stages.We also investigated its correlation with clinical outcomes,such as survival rates and drug sensitivity.Results:The results of our analysis showed significant deregulation of TOR1AIP1 expression in multiple cancer types and its association with clinical outcomes,with a particular emphasis on kidney renal clear cell carcinoma.The results of our study highlight the potential predictive value of TOR1AIP1 in cancer prognosis and therapy.Conclusions:This study establishes a solid foundation and rationale for future experimental investigations,which will contribute to a deeper under-standing of the significance of TOR1AIP1 in different cancer types,specifically in kidney renal clear cell carcinoma.展开更多
基金supported by a grant from the National Natural Science Foundation of China(31671390)funding from the Tsinghua-Peking Joint Center for Life Sciences。
文摘Apical actin filaments are highly dynamic structures that are crucial for rapid pollen tube growth, but the mechanisms regulating their dynamics and spatial organization remain incompletely understood. We here identify that AtAIP1-1 is important for regulating the turnover and organization of apical actin filaments in pollen tubes. AtAIP1-1 is distributed uniformly in the pollen tube and loss of function of AtAIP1-1 affects the organization of the actin cytoskeleton in the pollen tube. Specifically, actin filaments became disorganized within the apical region of aip1-1 pollen tubes. Consistent with the role of apical actin filaments in spatially restricting vesicles in pollen tubes, the apical region occupied by vesicles becomes enlarged in aip1-1 pollen tubes compared to WT. Using ADF1 as a representative actin-depolymerizing factor, we demonstrate that AtAIP1-1 enhances ADF1-mediated actin depolymerization and filament severing in vitro, although AtAIP1-1 alone does not have an obvious effect on actin assembly and disassembly. The dynamics of apical actin filaments are reduced in aip1-1 pollen tubes compared to WT. Our study suggests that AtAIP1-1 works together with ADF to act as a module in regulating the dynamics of apical actin filaments to facilitate the construction of the unique "apical actin structure" in the pollen tube.
文摘Background:Cancer poses a significant global challenge,and with the pro-jected rise in cancer incidence,there is an urgent need to discover new targets and treatments to improve patient outcomes.Recent advancements in geno-mics technologies have enhanced our understanding of cancer's complexities and led to the emergence of pan‐cancer analysis as a valuable approach for identifying tumor targets.Torsin‐1A‐interacting protein 1(TOR1AIP1)is a membrane protein involved in various cellular processes.Emerging evidence suggests its potential involvement in cancer.Methods:In this study,we conducted a comprehensive analysis of multiple databases to explore TOR1AIP1 expression across different cancer types and stages.We also investigated its correlation with clinical outcomes,such as survival rates and drug sensitivity.Results:The results of our analysis showed significant deregulation of TOR1AIP1 expression in multiple cancer types and its association with clinical outcomes,with a particular emphasis on kidney renal clear cell carcinoma.The results of our study highlight the potential predictive value of TOR1AIP1 in cancer prognosis and therapy.Conclusions:This study establishes a solid foundation and rationale for future experimental investigations,which will contribute to a deeper under-standing of the significance of TOR1AIP1 in different cancer types,specifically in kidney renal clear cell carcinoma.
