Astrocyte elevated gene-1 (AEG-1) was cloned as an human immunodeficiency virus -1-inducible and tumor necrosis factor-α-inducible transcript in primary human fetal astrocytes by a rapid subtraction hybridization app...Astrocyte elevated gene-1 (AEG-1) was cloned as an human immunodeficiency virus -1-inducible and tumor necrosis factor-α-inducible transcript in primary human fetal astrocytes by a rapid subtraction hybridization approach. AEG-1 down-regulates the expression of the glutamate transporter EAAT2,thus,it is implicated in glutamate-induced excitotoxic damage to neurons as evident in HIV-associated neurodegeneration. Meanwhile,AEG-1 expression is elevated in subsets of breast cancer,prostatic cancer,glioblastoma multiforme and melanoma cells,having a dual specificity phosphatase activity. Overexpression of AEG-1 increases and siRNA inhibition of AEG-1 decreases migration and invasion of human glioma cells,respectively. Recent observations indicate that AEG-1 exerts its effects by activating the nuclear factor kappa B (NF-κB) pathway and AEG-1 is a downstream target of Ha-ras and plays an important role in Ha-ras-mediated tumorigenesis. These findings are intensifying interest in AEG-1 as a crucial regulator of tumor progression and metastasis and as a potential mediator of neurodegeneration.展开更多
Objective This study aimed to investigate the effects of downregulating astrocyte elevated gene-1(AEG-1)expression combined with all-trans retinoic acid(ATRA)on vasculogenic mimicry(VM)formation and angiogenesis in gl...Objective This study aimed to investigate the effects of downregulating astrocyte elevated gene-1(AEG-1)expression combined with all-trans retinoic acid(ATRA)on vasculogenic mimicry(VM)formation and angiogenesis in glioma.Methods U87 glioma cells were transfected with AEG-1 shRNA lentiviral vectors(U87-siAEG-1)and incubated in a medium containing 20µmol/L ATRA.Matrigel-based tube formation assay was performed to evaluate VM formation,and the cell counting kit-8(CCK-8)assay was used to analyze the proliferation of glioma cells in vitro.Reverse transcription-quantitative polymerase chain reaction and Western blot analysis were used to investigate the mRNA and protein expression of related genes,respectively.Glioma xenograft models were generated via subcutaneous implantation of glioma cells in nude mice.Tumor-bearing mice received an intraperitoneal injection of ATRA(10 mg/kg per day).Immunohistochemistry was used to evaluate the expression of related genes and the microvessel density(MVD)in glioma xenograft models.CD34/periodic acid-Schiff double staining was performed to detect VM channels in vivo.The volume and weight of tumors were measured,and a tumor growth curve was drawn to evaluate tumor growth.Results A combination of ATRA intervention and downregulation of AEG-1 expression significantly inhibited the proliferation of glioma cells in vitro and glioma VM formation in vitro and in vivo.It also significantly decreased MVD and inhibited tumor growth.Further,the expression levels of matrix metalloproteinase(MMP)-2,MMP-9,vascular endothelial-cadherin(VE-cadherin),and vascular endothelial growth factor(VEGF)in glioma significantly decreased in vivo and in vivo.Conclusion Hence,a combinatorial approach might be effective in treating glioma through regulating MMP-2,MMP-9,VEGF,and VE-cadherin expression.展开更多
目的探讨敲低星形细胞上调基因-1(astrocyte elevated gene-1,AEG-1)表达对二乙基亚硝胺(diethylnitrosamine,DEN)诱导的原发性肝癌的调控。方法将60只大鼠随机分成Control组、DEN组、AEG-1 NC KO DEN组及AEG-1 KO DEN组,每组15只。除Co...目的探讨敲低星形细胞上调基因-1(astrocyte elevated gene-1,AEG-1)表达对二乙基亚硝胺(diethylnitrosamine,DEN)诱导的原发性肝癌的调控。方法将60只大鼠随机分成Control组、DEN组、AEG-1 NC KO DEN组及AEG-1 KO DEN组,每组15只。除Control组外,其余组均以DEN灌胃构建大鼠原发性肝癌模型,Control组和DEN组大鼠每日灌胃等体积生理盐水。AEG-1 KO DEN组和AEG-1 NC KO DEN组分别经腹腔注射稳定转染AEG-1shRNA或shRNA-NC慢病毒表达载体的HCCLM6。比较各组肝脏细胞损伤、凋亡、超氧化物歧化酶(superoxide dismutase,SOD)、丙二醛(malondialdehyde,MDA)和谷肽甘肽(glutathione peroxidase,GSH)、肝功能,血清IL-6、TNF-α含量,肝脏组织半胱氨酸蛋白酶3(caspase-3,Cas-3)、半胱氨酸蛋白酶9(caspase-9,Cas-9)表达及P65蛋白表达。结果DEN组AEG-1的表达水平明显高于Control组(P<0.05),AEG-1 KO DEN组的大鼠死亡率及腹水发生率低于DEN组(P<0.05);AEG-1 KO DEN组血清AST、ALT、IL-6和TNF-α水平低于DEN组(P<0.05),SOD活性高于DEN组(P<0.05),GSH和MDA含量低于DEN组(P<0.05),cleaved cas9/cas9、cleaved cas3/cas3和p-P65/P65蛋白表达低于DEN组(P<0.05)。结论AEG-1敲除可降低DEN诱导的大鼠的氧化应激水平以及炎症因子水平,减轻对肝脏组织的损伤,改善肝脏功能。展开更多
文摘Astrocyte elevated gene-1 (AEG-1) was cloned as an human immunodeficiency virus -1-inducible and tumor necrosis factor-α-inducible transcript in primary human fetal astrocytes by a rapid subtraction hybridization approach. AEG-1 down-regulates the expression of the glutamate transporter EAAT2,thus,it is implicated in glutamate-induced excitotoxic damage to neurons as evident in HIV-associated neurodegeneration. Meanwhile,AEG-1 expression is elevated in subsets of breast cancer,prostatic cancer,glioblastoma multiforme and melanoma cells,having a dual specificity phosphatase activity. Overexpression of AEG-1 increases and siRNA inhibition of AEG-1 decreases migration and invasion of human glioma cells,respectively. Recent observations indicate that AEG-1 exerts its effects by activating the nuclear factor kappa B (NF-κB) pathway and AEG-1 is a downstream target of Ha-ras and plays an important role in Ha-ras-mediated tumorigenesis. These findings are intensifying interest in AEG-1 as a crucial regulator of tumor progression and metastasis and as a potential mediator of neurodegeneration.
基金The present study was supported by grants from the Natural Science Foundation of Shaanxi Province(No.2017JQ8037)the Key Research and Development Plan of Shaanxi Province,China(No.2021SF-298)the National Natural Science Foundation of China(No.81572485).
文摘Objective This study aimed to investigate the effects of downregulating astrocyte elevated gene-1(AEG-1)expression combined with all-trans retinoic acid(ATRA)on vasculogenic mimicry(VM)formation and angiogenesis in glioma.Methods U87 glioma cells were transfected with AEG-1 shRNA lentiviral vectors(U87-siAEG-1)and incubated in a medium containing 20µmol/L ATRA.Matrigel-based tube formation assay was performed to evaluate VM formation,and the cell counting kit-8(CCK-8)assay was used to analyze the proliferation of glioma cells in vitro.Reverse transcription-quantitative polymerase chain reaction and Western blot analysis were used to investigate the mRNA and protein expression of related genes,respectively.Glioma xenograft models were generated via subcutaneous implantation of glioma cells in nude mice.Tumor-bearing mice received an intraperitoneal injection of ATRA(10 mg/kg per day).Immunohistochemistry was used to evaluate the expression of related genes and the microvessel density(MVD)in glioma xenograft models.CD34/periodic acid-Schiff double staining was performed to detect VM channels in vivo.The volume and weight of tumors were measured,and a tumor growth curve was drawn to evaluate tumor growth.Results A combination of ATRA intervention and downregulation of AEG-1 expression significantly inhibited the proliferation of glioma cells in vitro and glioma VM formation in vitro and in vivo.It also significantly decreased MVD and inhibited tumor growth.Further,the expression levels of matrix metalloproteinase(MMP)-2,MMP-9,vascular endothelial-cadherin(VE-cadherin),and vascular endothelial growth factor(VEGF)in glioma significantly decreased in vivo and in vivo.Conclusion Hence,a combinatorial approach might be effective in treating glioma through regulating MMP-2,MMP-9,VEGF,and VE-cadherin expression.
文摘目的探讨敲低星形细胞上调基因-1(astrocyte elevated gene-1,AEG-1)表达对二乙基亚硝胺(diethylnitrosamine,DEN)诱导的原发性肝癌的调控。方法将60只大鼠随机分成Control组、DEN组、AEG-1 NC KO DEN组及AEG-1 KO DEN组,每组15只。除Control组外,其余组均以DEN灌胃构建大鼠原发性肝癌模型,Control组和DEN组大鼠每日灌胃等体积生理盐水。AEG-1 KO DEN组和AEG-1 NC KO DEN组分别经腹腔注射稳定转染AEG-1shRNA或shRNA-NC慢病毒表达载体的HCCLM6。比较各组肝脏细胞损伤、凋亡、超氧化物歧化酶(superoxide dismutase,SOD)、丙二醛(malondialdehyde,MDA)和谷肽甘肽(glutathione peroxidase,GSH)、肝功能,血清IL-6、TNF-α含量,肝脏组织半胱氨酸蛋白酶3(caspase-3,Cas-3)、半胱氨酸蛋白酶9(caspase-9,Cas-9)表达及P65蛋白表达。结果DEN组AEG-1的表达水平明显高于Control组(P<0.05),AEG-1 KO DEN组的大鼠死亡率及腹水发生率低于DEN组(P<0.05);AEG-1 KO DEN组血清AST、ALT、IL-6和TNF-α水平低于DEN组(P<0.05),SOD活性高于DEN组(P<0.05),GSH和MDA含量低于DEN组(P<0.05),cleaved cas9/cas9、cleaved cas3/cas3和p-P65/P65蛋白表达低于DEN组(P<0.05)。结论AEG-1敲除可降低DEN诱导的大鼠的氧化应激水平以及炎症因子水平,减轻对肝脏组织的损伤,改善肝脏功能。
