Preclinical and clinical studies have shown that microglia and macrophages participate in a multiphasic brain damage repair process following intracerebral hemorrhage.The E26 transformation-specific sequence-related t...Preclinical and clinical studies have shown that microglia and macrophages participate in a multiphasic brain damage repair process following intracerebral hemorrhage.The E26 transformation-specific sequence-related transcription factor Spi1 regulates microglial/macrophage commitment and maturation.However,the effect of Spi1 on intracerebral hemorrhage remains unclear.In this study,we found that Spi1 may regulate recovery from the neuroinflammation and neurofunctional damage caused by intracerebral hemorrhage by modulating the microglial/macrophage transcriptome.We showed that high Spi1expression in microglia/macrophages after intracerebral hemorrhage is associated with the activation of many pathways that promote phagocytosis,glycolysis,and autophagy,as well as debris clearance and sustained remyelination.Notably,microglia with higher levels of Soil expression were chara cterized by activation of pathways associated with a variety of hemorrhage-related cellular processes,such as complement activation,angiogenesis,and coagulation.In conclusion,our results suggest that Spi1 plays a vital role in the microglial/macrophage inflammatory response following intracerebral hemorrhage.This new insight into the regulation of Spi1 and its target genes may advance our understanding of neuroinflammation in intracerebral hemorrhage and provide therapeutic targets for patients with intracerebral hemorrhage.展开更多
Background:Glioma is a common malignant brain tumor.The purpose of this study was to investigate the role of the transcription factor SPI1 in glioma.Methods:SPI1 expression in glioma was identified using qRT-PCR and W...Background:Glioma is a common malignant brain tumor.The purpose of this study was to investigate the role of the transcription factor SPI1 in glioma.Methods:SPI1 expression in glioma was identified using qRT-PCR and Western blotting.Cell proliferation was assessed using the CCK8 assay.Transwell and wound healing assays were utilized to evaluate cell migration.Additionally,cell cycle and apoptosis were detected using flow cytometry.Results:We observed that the expression level of SPI1 was up-regulated in glioma tissues,compared to normal tissues.Furthermore,we found that SPI1 is able to promote proliferation and migration of glioma cells in vitro.Flow cytometry results demonstrate that,compared to si-NC cells,si-SPI1 cells stagnated in the G1 phase,and downregulation of SPI1 expression is able to increase rates of apoptosis.Double luciferase activity and chromatin immunoprecipitation assay results indicated that SPI1 can bind to the promoter sites and promote the proliferation and migration of glioma cells by regulating the expression of oncogenic PAICS.Conclusions:Our results suggest that SPI1 can promote proliferation and migration of glioma.Furthermore,SPI1 can be utilized as a potential diagnostic marker and therapeutic target for glioma.展开更多
基金supported by the National Natural Science Foundation of China,No.81971097(to JY)。
文摘Preclinical and clinical studies have shown that microglia and macrophages participate in a multiphasic brain damage repair process following intracerebral hemorrhage.The E26 transformation-specific sequence-related transcription factor Spi1 regulates microglial/macrophage commitment and maturation.However,the effect of Spi1 on intracerebral hemorrhage remains unclear.In this study,we found that Spi1 may regulate recovery from the neuroinflammation and neurofunctional damage caused by intracerebral hemorrhage by modulating the microglial/macrophage transcriptome.We showed that high Spi1expression in microglia/macrophages after intracerebral hemorrhage is associated with the activation of many pathways that promote phagocytosis,glycolysis,and autophagy,as well as debris clearance and sustained remyelination.Notably,microglia with higher levels of Soil expression were chara cterized by activation of pathways associated with a variety of hemorrhage-related cellular processes,such as complement activation,angiogenesis,and coagulation.In conclusion,our results suggest that Spi1 plays a vital role in the microglial/macrophage inflammatory response following intracerebral hemorrhage.This new insight into the regulation of Spi1 and its target genes may advance our understanding of neuroinflammation in intracerebral hemorrhage and provide therapeutic targets for patients with intracerebral hemorrhage.
基金National Natural Science Foundation of China(Grant No.81802470)Joint construction project of Henan Medical Science and technology research plan(Grant No.LHGJ20190452)+1 种基金the Doctoral Scientific Research Foundation of Xinxiang Medical University(Grant No.XYBSKYZZ201632)Natural Science Foundation of Henan Province(Grant No.202300410326)
文摘Background:Glioma is a common malignant brain tumor.The purpose of this study was to investigate the role of the transcription factor SPI1 in glioma.Methods:SPI1 expression in glioma was identified using qRT-PCR and Western blotting.Cell proliferation was assessed using the CCK8 assay.Transwell and wound healing assays were utilized to evaluate cell migration.Additionally,cell cycle and apoptosis were detected using flow cytometry.Results:We observed that the expression level of SPI1 was up-regulated in glioma tissues,compared to normal tissues.Furthermore,we found that SPI1 is able to promote proliferation and migration of glioma cells in vitro.Flow cytometry results demonstrate that,compared to si-NC cells,si-SPI1 cells stagnated in the G1 phase,and downregulation of SPI1 expression is able to increase rates of apoptosis.Double luciferase activity and chromatin immunoprecipitation assay results indicated that SPI1 can bind to the promoter sites and promote the proliferation and migration of glioma cells by regulating the expression of oncogenic PAICS.Conclusions:Our results suggest that SPI1 can promote proliferation and migration of glioma.Furthermore,SPI1 can be utilized as a potential diagnostic marker and therapeutic target for glioma.
文摘[目的]探讨抑制Spy1表达后食管癌细胞对化疗药物顺铂敏感性的变化。[方法]在食管癌Eca-109细胞中转染靶向Spy1的si RNA,采用RT-PCR和Western Blot检测Spy1的表达情况;MTT法检测抑制Spy1表达后对Eca-109细胞生长和对顺铂化疗敏感性的影响;流式细胞术检测干扰Spy1对细胞周期的影响。[结果]转染Spy1 si RNA后,食管癌Eca-109细胞中Spy1的m RNA和蛋白水平明显下降;MTT结果显示顺铂对Eca-109细胞的半数抑制浓度(50%inhibiting concentration,IC50)由4.56±1.23μg/ml降至1.12±0.09μg/ml;转染Spy1 si RNA联合顺铂IC50处理使细胞存活率由(64.7±3.8)%降至(46.8±4.2)%;细胞周期更多阻滞于G0/G1期(P<0.05)。[结论]靶向干扰Spy1表达可抑制食管癌细胞的生长,增强顺铂对肿瘤细胞的杀伤作用,其机制与细胞阻滞于G0/G1期有关。
文摘目的:探讨SPY1(Speedy A1)和p27^(kip1)(cyclin-dependent kinase inhibitor 1B,p27)在子宫内膜癌中的表达情况及其临床意义。方法:采用生物医学信息数据库分析子宫内膜癌中SPY1、p27^(kip1) mRNA表达水平;采用免疫组织化学染色法及蛋白质印迹法检测子宫内膜癌及正常子宫内膜组织中SPY1、p27^(kip1)蛋白的表达水平,并分析其表达与患者临床病理参数、激素受体、癌症基因组图谱分子分型的关系,以及两者之间的相关性。通过Kaplan-Meier法绘制生存曲线,应用Cox比例风险模型分析影响子宫内膜癌患者的预后因素。结果:SPY1在子宫内膜癌组织中的蛋白质表达水平显著高于不典型增生的子宫内膜及正常子宫内膜组织(P=0.009),p27kip1在子宫内膜癌组织中的蛋白质表达水平显著低于不典型增生的子宫内膜及正常子宫内膜组织(P=0.001);SPY1蛋白表达与肿瘤病理分级(P=0.023)、国际妇产科协会(The International Federation of Gynecology and Obstetrics,FIGO)癌分期(P=0.003),肌层浸润深度(P=0.010)及淋巴结转移(P<0.001)有关,p27kip1蛋白表达与肿瘤病理分级(P=0.001)、FIGO癌分期(P=0.001)及淋巴结转移(P<0.001)有关;SPY1与p27kip1表达呈负相关(r=−0.563,P<0.001);Kaplan-Meier预后分析表明SPY1高表达患者生存率低于低表达患者(P<0.05),p27kip1高表达患者的生存率高于低表达患者(P<0.05)。Cox单因素及多因素分析表明FIGO癌分期(P=0.023)、病理分级(P<0.001)、淋巴结转移(P<0.001)及p27kip1表达(P<0.001)可作为子宫内膜癌患者的独立预后指标。结论:子宫内膜癌组织中SPY1蛋白呈高表达,p27kip1蛋白呈低表达,且两者之间呈负相关,可用于评估子宫内膜癌的发生和发展。
