Xue Cui - Academia.edu (original) (raw)
Papers by Xue Cui
Journal of Thrombosis and Haemostasis, Feb 1, 2016
Thrombosis Research, Sep 1, 2017
Hypoxia is one of the most pervasive physiological stresses in solid tumors. We have previously d... more Hypoxia is one of the most pervasive physiological stresses in solid tumors. We have previously demonstrated that tissue factor (TF) pathway inhibitor (TFPI) expression was transcriptionally repressed by the activation of hypoxia inducible factor (HIF)-1α under hypoxic conditions. However, the role of HIF-2α, also known as endothelial PAS domain-containing protein 1 (EPAS1), on TFPI expression remains unclear. To explore the role of HIF-2α/EPAS1 in the regulation of TFPI expression under hypoxia in breast cancer cells. Quantitative RT-PCR showed that total TFPI mRNA and protein levels were decreased by the overexpression of HIF-2α/EPAS1 in MCF7 cells. Luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay indicated a HIF-2α/EPAS1 responsive region located in the TFPI promoter region at -170 to +21 relative to the transcriptional start site. Subsequent mutagenesis demonstrated a functional hypoxia response element (HRE) 5'-AAACAGGA-3' for HIF-2α/EPAS1 within the TFPI promoter located at -45 to -38. In breast cancer patients, a positive correlation between HIF-2α/EPAS1 and total TFPI mRNA expression was observed by using gene expression analysis. This study provides evidence that HIF-2α/EPAS1 is involved in the regulation of TFPI gene expression in breast cancer cells, suggesting that the activation of coagulation and the increased risk of thrombosis observed in breast cancer patients may correlate with local hypoxic regulation of coagulation factors and their inhibitors.
International Journal of Molecular Sciences, Nov 8, 2022
International Journal of Molecular Sciences
Factor-VII-activating protease (FSAP) is involved in the regulation of hemostasis and inflammatio... more Factor-VII-activating protease (FSAP) is involved in the regulation of hemostasis and inflammation. Extracellular histones play a role in inflammation and the conversion of latent pro-FSAP into active FSAP. FSAP has been shown to regulate endothelial permeability, but the mechanisms are not clear. Here, we have investigated the effects of FSAP on endothelial permeability in vitro. A mixture of histones from calf thymus stimulated permeability, and the wild-type (WT) serine protease domain (SPD) of FSAP blocked this effect. WT–SPD–FSAP did not influence permeability on its own, nor that stimulated by thrombin or vascular endothelial growth factor (VEGF)-A165. Histones induced a large-scale rearrangement of the junction proteins VE-cadherin and zona occludens-1 from a clear junctional distribution to a diffuse pattern. The presence of WT–SPD–FSAP inhibited these changes. Permeability changes by histones were blocked by both TLR-2 and TLR4 blocking antibodies. Histones upregulated the ...
Scientific Reports, 2021
The infiltration of chronic lymphocytic leukemia (CLL) cells into lymphoid organs correlates with... more The infiltration of chronic lymphocytic leukemia (CLL) cells into lymphoid organs correlates with disease severity. CXCL12 is a key chemotactic factor for the trafficking of CLL. Tissue factor pathway inhibitor (TFPI) is a serine protease inhibitor and plays a role in CXCL12-mediated hematopoietic stem cell homing. We aim to explore the role of TFPI in CXCL12-mediated migration of CLL cells. In this study, plasma TFPI concentrations were measured by ELISA. CLL cells were isolated from patients and used for trans-endothelial migration (TEM) assays. Quantitative RT-PCR and Western blotting were used to detect the expression of CXCR7, CXCR4 and β-catenin. Immunofluorescence and co-immunoprecipitation was used to detect the binding of TFPI and glypican-3 (GPC3). We found that plasma TFPI levels in CLL patients were higher than in healthy controls, particularly in the patients with advanced disease. TFPI enhanced CXCL12-mediated TEM of CLL cells by increasing the expression of the CXCL12...
Journal of thrombosis and haemostasis : JTH, Jan 24, 2015
Activation of coagulation is a common finding in patients with cancer, and is associated with inc... more Activation of coagulation is a common finding in patients with cancer, and is associated with increased risk of venous thrombosis. Since hypoxic microenvironment is a common feature of solid tumors, we investigated the role of hypoxia in the regulation of tissue factor (TF) pathway inhibitor (TFPI) expression in breast cancer. To explore the transcriptional regulation of TFPI by hypoxia inducible factor 1α (HIF-1α) in breast cancer cells and their correlations in breast cancer tissues. MCF-7 and SK-BR-3 breast cancer cells were cultured in 1% oxygen tension or treated with cobalt chloride (CoCl2 ) to mimic hypoxia. A time- and dose-dependent downregulation of TFPI mRNA by quantitative RT-PCR and of free TFPI protein by ELISA assay was observed in hypoxia. Western blot showed the parallel increase of hypoxia inducible factor (HIF) 1α protein and TF. HIF-1α inhibitor abolished or attenuated hypoxia-induced downregulation of TFPI. Luciferase reporter assay showed that both hypoxia and ...
Proceedings of the …, 1992
We have developed an in vitro method for amplifying a large fraction of the DNA sequences present... more We have developed an in vitro method for amplifying a large fraction of the DNA sequences present in a single haploid cell by repeated primer extensions using a mixture of 15-base random oligonucleotides. We studied 12 genetic loci and estimate that the ...
Biochimica et biophysica acta, Jan 26, 2016
Neovascularization and hemorrhaging are evident in advanced atherosclerotic plaques due to hypoxi... more Neovascularization and hemorrhaging are evident in advanced atherosclerotic plaques due to hypoxic conditions, and mediate the accumulation of metabolic substrates, inflammatory cells, lipids, and other blood born factors inside the plaque. Tissue factor (TF) pathway inhibitor (TFPI) is mainly expressed by endothelial cells and is the endogenous inhibitor of the coagulation activator TF, which together with the downstream product thrombin can drive plaque progression and atherogenesis. We aimed to investigate the effect of hypoxic conditions on endothelial cell expression and activity of TFPI and TF that are important in coagulation initiation. Hypoxia was induced in primary human umbilical vein endothelial cells using chemicals or 1% oxygen tension, and mRNA and protein expressions were measured using qRT-PCR, ELISA, and Western blot analysis. Microscopy of fluorescence-labeled cells was used to visualize cell-associated TFPI. Cell-surface factor Xa (FXa) activity was measured usin...
Journal of thrombosis and haemostasis : JTH, Jan 24, 2015
Activation of coagulation is a common finding in patients with cancer, and is associated with inc... more Activation of coagulation is a common finding in patients with cancer, and is associated with increased risk of venous thrombosis. Since hypoxic microenvironment is a common feature of solid tumors, we investigated the role of hypoxia in the regulation of tissue factor (TF) pathway inhibitor (TFPI) expression in breast cancer. To explore the transcriptional regulation of TFPI by hypoxia inducible factor 1α (HIF-1α) in breast cancer cells and their correlations in breast cancer tissues. MCF-7 and SK-BR-3 breast cancer cells were cultured in 1% oxygen tension or treated with cobalt chloride (CoCl2 ) to mimic hypoxia. A time- and dose-dependent downregulation of TFPI mRNA by quantitative RT-PCR and of free TFPI protein by ELISA assay was observed in hypoxia. Western blot showed the parallel increase of hypoxia inducible factor (HIF) 1α protein and TF. HIF-1α inhibitor abolished or attenuated hypoxia-induced downregulation of TFPI. Luciferase reporter assay showed that both hypoxia and ...
Journal of Thrombosis and Haemostasis, Feb 1, 2016
Thrombosis Research, Sep 1, 2017
Hypoxia is one of the most pervasive physiological stresses in solid tumors. We have previously d... more Hypoxia is one of the most pervasive physiological stresses in solid tumors. We have previously demonstrated that tissue factor (TF) pathway inhibitor (TFPI) expression was transcriptionally repressed by the activation of hypoxia inducible factor (HIF)-1α under hypoxic conditions. However, the role of HIF-2α, also known as endothelial PAS domain-containing protein 1 (EPAS1), on TFPI expression remains unclear. To explore the role of HIF-2α/EPAS1 in the regulation of TFPI expression under hypoxia in breast cancer cells. Quantitative RT-PCR showed that total TFPI mRNA and protein levels were decreased by the overexpression of HIF-2α/EPAS1 in MCF7 cells. Luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay indicated a HIF-2α/EPAS1 responsive region located in the TFPI promoter region at -170 to +21 relative to the transcriptional start site. Subsequent mutagenesis demonstrated a functional hypoxia response element (HRE) 5'-AAACAGGA-3' for HIF-2α/EPAS1 within the TFPI promoter located at -45 to -38. In breast cancer patients, a positive correlation between HIF-2α/EPAS1 and total TFPI mRNA expression was observed by using gene expression analysis. This study provides evidence that HIF-2α/EPAS1 is involved in the regulation of TFPI gene expression in breast cancer cells, suggesting that the activation of coagulation and the increased risk of thrombosis observed in breast cancer patients may correlate with local hypoxic regulation of coagulation factors and their inhibitors.
International Journal of Molecular Sciences, Nov 8, 2022
International Journal of Molecular Sciences
Factor-VII-activating protease (FSAP) is involved in the regulation of hemostasis and inflammatio... more Factor-VII-activating protease (FSAP) is involved in the regulation of hemostasis and inflammation. Extracellular histones play a role in inflammation and the conversion of latent pro-FSAP into active FSAP. FSAP has been shown to regulate endothelial permeability, but the mechanisms are not clear. Here, we have investigated the effects of FSAP on endothelial permeability in vitro. A mixture of histones from calf thymus stimulated permeability, and the wild-type (WT) serine protease domain (SPD) of FSAP blocked this effect. WT–SPD–FSAP did not influence permeability on its own, nor that stimulated by thrombin or vascular endothelial growth factor (VEGF)-A165. Histones induced a large-scale rearrangement of the junction proteins VE-cadherin and zona occludens-1 from a clear junctional distribution to a diffuse pattern. The presence of WT–SPD–FSAP inhibited these changes. Permeability changes by histones were blocked by both TLR-2 and TLR4 blocking antibodies. Histones upregulated the ...
Scientific Reports, 2021
The infiltration of chronic lymphocytic leukemia (CLL) cells into lymphoid organs correlates with... more The infiltration of chronic lymphocytic leukemia (CLL) cells into lymphoid organs correlates with disease severity. CXCL12 is a key chemotactic factor for the trafficking of CLL. Tissue factor pathway inhibitor (TFPI) is a serine protease inhibitor and plays a role in CXCL12-mediated hematopoietic stem cell homing. We aim to explore the role of TFPI in CXCL12-mediated migration of CLL cells. In this study, plasma TFPI concentrations were measured by ELISA. CLL cells were isolated from patients and used for trans-endothelial migration (TEM) assays. Quantitative RT-PCR and Western blotting were used to detect the expression of CXCR7, CXCR4 and β-catenin. Immunofluorescence and co-immunoprecipitation was used to detect the binding of TFPI and glypican-3 (GPC3). We found that plasma TFPI levels in CLL patients were higher than in healthy controls, particularly in the patients with advanced disease. TFPI enhanced CXCL12-mediated TEM of CLL cells by increasing the expression of the CXCL12...
Journal of thrombosis and haemostasis : JTH, Jan 24, 2015
Activation of coagulation is a common finding in patients with cancer, and is associated with inc... more Activation of coagulation is a common finding in patients with cancer, and is associated with increased risk of venous thrombosis. Since hypoxic microenvironment is a common feature of solid tumors, we investigated the role of hypoxia in the regulation of tissue factor (TF) pathway inhibitor (TFPI) expression in breast cancer. To explore the transcriptional regulation of TFPI by hypoxia inducible factor 1α (HIF-1α) in breast cancer cells and their correlations in breast cancer tissues. MCF-7 and SK-BR-3 breast cancer cells were cultured in 1% oxygen tension or treated with cobalt chloride (CoCl2 ) to mimic hypoxia. A time- and dose-dependent downregulation of TFPI mRNA by quantitative RT-PCR and of free TFPI protein by ELISA assay was observed in hypoxia. Western blot showed the parallel increase of hypoxia inducible factor (HIF) 1α protein and TF. HIF-1α inhibitor abolished or attenuated hypoxia-induced downregulation of TFPI. Luciferase reporter assay showed that both hypoxia and ...
Proceedings of the …, 1992
We have developed an in vitro method for amplifying a large fraction of the DNA sequences present... more We have developed an in vitro method for amplifying a large fraction of the DNA sequences present in a single haploid cell by repeated primer extensions using a mixture of 15-base random oligonucleotides. We studied 12 genetic loci and estimate that the ...
Biochimica et biophysica acta, Jan 26, 2016
Neovascularization and hemorrhaging are evident in advanced atherosclerotic plaques due to hypoxi... more Neovascularization and hemorrhaging are evident in advanced atherosclerotic plaques due to hypoxic conditions, and mediate the accumulation of metabolic substrates, inflammatory cells, lipids, and other blood born factors inside the plaque. Tissue factor (TF) pathway inhibitor (TFPI) is mainly expressed by endothelial cells and is the endogenous inhibitor of the coagulation activator TF, which together with the downstream product thrombin can drive plaque progression and atherogenesis. We aimed to investigate the effect of hypoxic conditions on endothelial cell expression and activity of TFPI and TF that are important in coagulation initiation. Hypoxia was induced in primary human umbilical vein endothelial cells using chemicals or 1% oxygen tension, and mRNA and protein expressions were measured using qRT-PCR, ELISA, and Western blot analysis. Microscopy of fluorescence-labeled cells was used to visualize cell-associated TFPI. Cell-surface factor Xa (FXa) activity was measured usin...
Journal of thrombosis and haemostasis : JTH, Jan 24, 2015
Activation of coagulation is a common finding in patients with cancer, and is associated with inc... more Activation of coagulation is a common finding in patients with cancer, and is associated with increased risk of venous thrombosis. Since hypoxic microenvironment is a common feature of solid tumors, we investigated the role of hypoxia in the regulation of tissue factor (TF) pathway inhibitor (TFPI) expression in breast cancer. To explore the transcriptional regulation of TFPI by hypoxia inducible factor 1α (HIF-1α) in breast cancer cells and their correlations in breast cancer tissues. MCF-7 and SK-BR-3 breast cancer cells were cultured in 1% oxygen tension or treated with cobalt chloride (CoCl2 ) to mimic hypoxia. A time- and dose-dependent downregulation of TFPI mRNA by quantitative RT-PCR and of free TFPI protein by ELISA assay was observed in hypoxia. Western blot showed the parallel increase of hypoxia inducible factor (HIF) 1α protein and TF. HIF-1α inhibitor abolished or attenuated hypoxia-induced downregulation of TFPI. Luciferase reporter assay showed that both hypoxia and ...