Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA158997 | ENA |
REPOSITORIES: ENA
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Project description:Abstract: Background & Aims: Unusual hypervascularity is a hallmark of human hepatocellular carcinoma (HCC). Although microRNA-214 (miR-214) is upregulated in other human cancers, it is downregulated in HCC. We elucidated the biological and clinical significance of miR-214 downregulation in HCC. Methods: MicroRNAs deregulated in HCC were identified using array-based MicroRNA profiling. A luciferase reporter assay confirmed target association between miR-214 and hepatoma-derived growth factor (HDGF). Tube formation and in vivo angiogenesis assays validated the roles of miR-214/HDGF in angiogenesis. Results: MiR-214 downregulation was associated with higher tumor recurrence and worse clinical outcomes. Ectopic expression of miR-214 suppressed xenograft tumor growth and microvascularity of the tumor and its surrounding tissues. The genes downregulated by ectopic expression of miR-214 were involved in the regulation of apoptosis, cell cycle, and angiogenesis. Integrated analysis disclosed HDGF as a downstream target of miR-214. Conditioned medium of HCC cells contained bioactivity to stimulate tube formation of human umbilical vein endothelial cells, which was abolished by pretreatment of the conditioned media with HDGF antibodies, silencing of HDGF expression or ectopic expression of miR-214 in the donor HCC cells. The angiogenic activity of the conditioned media lost by ectopic expression of miR-214 in the donor cells was restored by supplementation with recombinant HDGF. In vivo tumor angiogenesis assays showed significant suppression of tumor vascularity by ectopic expression of miR-214. Conclusions: A novel role of microRNA in tumrigenesis is identified. Downregulation of miR-214 contributes to unusual hypervascularity of HCC via activation of the HDGF paracrine pathway for tumor angiogenesis. To identify miRNAs that are deregulated in human HCC, 68 HCC and 21 non-tumor liver tissues were subjected to profiling of miRNA expression using miRNA arrays containing 739 human miRNA probes. Differentially expressed microRNAs were identified.
2013-04-01 | E-GEOD-36915 | biostudies-arrayexpress
Project description:Abstract: Background & Aims: Unusual hypervascularity is a hallmark of human hepatocellular carcinoma (HCC). Although microRNA-214 (miR-214) is upregulated in other human cancers, it is downregulated in HCC. We elucidated the biological and clinical significance of miR-214 downregulation in HCC. Methods: MicroRNAs deregulated in HCC were identified using array-based MicroRNA profiling. A luciferase reporter assay confirmed target association between miR-214 and hepatoma-derived growth factor (HDGF). Tube formation and in vivo angiogenesis assays validated the roles of miR-214/HDGF in angiogenesis. Results: MiR-214 downregulation was associated with higher tumor recurrence and worse clinical outcomes. Ectopic expression of miR-214 suppressed xenograft tumor growth and microvascularity of the tumor and its surrounding tissues. The genes downregulated by ectopic expression of miR-214 were involved in the regulation of apoptosis, cell cycle, and angiogenesis. Integrated analysis disclosed HDGF as a downstream target of miR-214. Conditioned medium of HCC cells contained bioactivity to stimulate tube formation of human umbilical vein endothelial cells, which was abolished by pretreatment of the conditioned media with HDGF antibodies, silencing of HDGF expression or ectopic expression of miR-214 in the donor HCC cells. The angiogenic activity of the conditioned media lost by ectopic expression of miR-214 in the donor cells was restored by supplementation with recombinant HDGF. In vivo tumor angiogenesis assays showed significant suppression of tumor vascularity by ectopic expression of miR-214. Conclusions: A novel role of microRNA in tumrigenesis is identified. Downregulation of miR-214 contributes to unusual hypervascularity of HCC via activation of the HDGF paracrine pathway for tumor angiogenesis.
2013-04-01 | GSE36915 | GEO
Project description:The platelet-derived growth factor (PDGF) signaling system contributes to tumor angiogenesis and vascular remodeling. Here, we show PDGF-BB markedly induces erythropoietin (EPO) mRNA and protein expression by targeting the PDGFR-beta+ stromal and perivascular compartments. In mouse tumor models, PDGF-BB-induced EPO promotes tumor growth via two mechanisms: 1) paracrine stimulation of tumor angiogenesis by directly inducing endothelial cell proliferation, migration, sprouting and tube formation; and 2) endocrine stimulation of extramedullary hematopoiesis leading to increased oxygen perfusion and protection against tumor-associated anemia. Similarly, delivery of an adenovirus-PDGF-BB to tumor-free mice markedly increases EPO production and hematopoietic parameters. An EPO blockade specifically attenuates PDGF-BB-induced tumor growth, angiogenesis and hematopoiesis. At the molecular level, we show that the PDGF-BB-PDGFR-beta signaling system activates EPO promoter via in part transcriptional regulation of ATF3 by possible association with c-Jun and SP1. These findings uncover a novel mechanism of PDGF-BB-induced tumor growth, angiogenesis and hematopoiesis. Comparison of S17 stromal cells treated with PDGF-BB for 72h to control
2011-12-04 | E-GEOD-33717 | biostudies-arrayexpress
Project description:Role of MicroRNA-214 in Ginsenoside-Rg1-induced Angiogenesis
| PRJNA118533 | ENA
Project description:Signalling between endothelial cells, endothelial progenitor cells and stromal cells is crucial for the establishment and maintenance of vascular integrity and involves exosomes, among other signalling pathways. Exosomes are important mediators of intercellular communication in immune signalling, tumour survival, stress responses and angiogenesis. The ability of exosomes to incorporate and transfer mRNAs encoding for ‘acquired’ proteins or miRNAs repressing ‘resident’ mRNA translation suggests that they can influence the physiological behaviour of recipient cells. We here demonstrate that miR-214, a miRNA that controls endothelial cell function and angiogenesis, plays a dominant role in exosome-mediated signalling between endothelial cells. Endothelial cell-derived exosomes stimulated migration and angiogenesis in recipient cells, whereas exosomes from miR-214 depleted endothelial cells failed to stimulate these processes. Exosomes containing miR-214 repressed the expression of Ataxia Telangiectasia Mutated in recipient cells, thereby preventing senescence and allowing blood vessel formation. Concordantly, specific reduction of miR-214 content in exosome-producing endothelial cells abolishes the angiogenesis the angiogenesis stimulatory function of the resulting exosomes. Collectively our data indicate that endothelial cells release miR-214 containing exosomes to stimulate angiogenesis through silencing of Ataxia Telangiectasia Mutated in neighbouring target cells. Gene expression analysis of HMEC endothelial cells exposed to supernatant containing either HMEC derived exosomes (miR-214 high), HMEC derived exosomes depleted of miR-214 (miR-214 low) or containing no exosomes (no exosomes). Each sample was analysed in duplo.
2013-03-22 | E-GEOD-45375 | biostudies-arrayexpress
Project description:The platelet-derived growth factor (PDGF) signaling system contributes to tumor angiogenesis and vascular remodeling. Here, we show PDGF-BB markedly induces erythropoietin (EPO) mRNA and protein expression by targeting the PDGFR-beta+ stromal and perivascular compartments. In mouse tumor models, PDGF-BB-induced EPO promotes tumor growth via two mechanisms: 1) paracrine stimulation of tumor angiogenesis by directly inducing endothelial cell proliferation, migration, sprouting and tube formation; and 2) endocrine stimulation of extramedullary hematopoiesis leading to increased oxygen perfusion and protection against tumor-associated anemia. Similarly, delivery of an adenovirus-PDGF-BB to tumor-free mice markedly increases EPO production and hematopoietic parameters. An EPO blockade specifically attenuates PDGF-BB-induced tumor growth, angiogenesis and hematopoiesis. At the molecular level, we show that the PDGF-BB-PDGFR-beta signaling system activates EPO promoter via in part transcriptional regulation of ATF3 by possible association with c-Jun and SP1. These findings uncover a novel mechanism of PDGF-BB-induced tumor growth, angiogenesis and hematopoiesis.
2011-12-04 | GSE33717 | GEO
Project description:Signalling between endothelial cells, endothelial progenitor cells and stromal cells is crucial for the establishment and maintenance of vascular integrity and involves exosomes, among other signalling pathways. Exosomes are important mediators of intercellular communication in immune signalling, tumour survival, stress responses and angiogenesis. The ability of exosomes to incorporate and transfer mRNAs encoding for ‘acquired’ proteins or miRNAs repressing ‘resident’ mRNA translation suggests that they can influence the physiological behaviour of recipient cells. We here demonstrate that miR-214, a miRNA that controls endothelial cell function and angiogenesis, plays a dominant role in exosome-mediated signalling between endothelial cells. Endothelial cell-derived exosomes stimulated migration and angiogenesis in recipient cells, whereas exosomes from miR-214 depleted endothelial cells failed to stimulate these processes. Exosomes containing miR-214 repressed the expression of Ataxia Telangiectasia Mutated in recipient cells, thereby preventing senescence and allowing blood vessel formation. Concordantly, specific reduction of miR-214 content in exosome-producing endothelial cells abolishes the angiogenesis the angiogenesis stimulatory function of the resulting exosomes. Collectively our data indicate that endothelial cells release miR-214 containing exosomes to stimulate angiogenesis through silencing of Ataxia Telangiectasia Mutated in neighbouring target cells.
2013-03-22 | GSE45375 | GEO
Project description:MicroRNAs (miRNAs) are small non-coding RNAs that act as post-transcriptional gene modulators. Ginsenoside-Rg1, one of the active components of ginseng, has been confirmed by us as an angiogenesis inducer. Using miRNA microarray analysis, a total of 15 (including miR-214) and 3 miRNAs were found to be down- or up-regulated by Rg1 in human umbilical vein endothelial cells (HUVEC), respectively. Since miR-214 is closely related to endothelial nitric oxide synthase (eNOS) and hence angiogenesis; its expression was further validated by qRT-PCR. We also investigated the role of miR-214 on eNOS expression and in tubulogenesis of HUVEC by transfection of specific miRNA inhibitor or precursor. Our results suggested that Rg1 can down-regulate miR-214 expression in HUVEC, leading to an increase in eNOS expression which can promote angiogenesis. This result signifies a new understanding towards how a simple natural compound can affect physiological changes through modulation of miRNA expression. The study is used to investigate the role of miRNA-214 in Rg1-induced human endothelial cells.
2010-08-05 | E-GEOD-17541 | biostudies-arrayexpress
Project description:A key step in angiogenesis is the upregulation of growth factor receptors on endothelial cells. Here we demonstrate that a small regulatory microRNA, miR-296 has a major role in this process. Glioma cells and angiogenic growth factors elevate the level of miR-296 in primary human brain microvascular endothelial cells in culture. The miR-296 level is also elevated in primary tumor endothelial cells isolated from human brain tumors compared to normal brain endothelial cells. Growth factor-induced miR-296 contributes significantly to angiogenesis by directly targeting the hepatocyte growth factor-regulated tyrosine kinase substrate (HGS) mRNA, leading to decreased levels of HGS and thereby reducing HGS-mediated degradation of the growth factor receptors VEGFR2 and PDGFR-β. Furthermore, inhibition of miR-296 with antagomirs reduces angiogenesis in tumor xenografts in vivo. Keywords: comparitive miRNA analysis 3 biological replicates (HBMVECs) are compared to 3 biological replicates (HBMVECs exposed to U87 glioma cells)
2010-06-25 | E-GEOD-13091 | biostudies-arrayexpress
Project description:MicroRNAs (miRNAs) are small non-coding RNAs that act as post-transcriptional gene modulators. Ginsenoside-Rg1, one of the active components of ginseng, has been confirmed by us as an angiogenesis inducer. Using miRNA microarray analysis, a total of 15 (including miR-214) and 3 miRNAs were found to be down- or up-regulated by Rg1 in human umbilical vein endothelial cells (HUVEC), respectively. Since miR-214 is closely related to endothelial nitric oxide synthase (eNOS) and hence angiogenesis; its expression was further validated by qRT-PCR. We also investigated the role of miR-214 on eNOS expression and in tubulogenesis of HUVEC by transfection of specific miRNA inhibitor or precursor. Our results suggested that Rg1 can down-regulate miR-214 expression in HUVEC, leading to an increase in eNOS expression which can promote angiogenesis. This result signifies a new understanding towards how a simple natural compound can affect physiological changes through modulation of miRNA expression.
2010-08-05 | GSE17541 | GEO