Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA193590 | ENA |
REPOSITORIES: ENA
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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: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: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:P16Ink4a is a well-established marker of senescence. Although P16Ink4a is expressed in endothelial cells, little is known about its function in these cells. Using isolated liver endothelial cells with silencing or overexpression of P16Ink4a, we show here that dependent on P16Ink4a levels, different pathways and functions are affected. High levels of P16Ink4a reduce proliferation and induce senescence while low levels have the opposite effects. Only high P16Ink4a expression reduces in vitro angiogenesis. Expression profiling reveals an inflammatory phenotype upon silencing of P16Ink4a while P16Ink4a overexpression is associated with a profile associated to DNA damage, repair and senescence. Low levels of P16Ink4a induce reactive oxygen species (ROS) generation and increase endothelial cell leakage. Collectively, P16Ink4a represents an “antagonistic pleiotropy” gene, which is on the one hand required to prevent ROS generation and endothelial damage and on the other hand at high levels inhibits angiogenesis through induction of senescence.
2024-11-18 | GSE281665 | GEO
Project description:Background: Docosahexaenoic acid (DHA) is a natural compound with anticancer and anti-angiogenesis activity that is currently under investigation as both a preventative agent and an adjuvant to breast cancer therapy. However, the precise mechanisms of DHA’s anticancer activities are unclear. It is understood that the intercommunication between cancer cells and their microenvironment is essential to tumor angiogenesis. Exosomes are extracellular vesicles that are important mediators of intercellular communication and play a role in promoting angiogenesis. However, very little is known about the contribution of breast cancer exosomes to tumor angiogenesis or whether exosomes can mediate DHA’s anticancer action. Results: Exosomes were collected from MCF7 and MDA-MB-231 breast cancer cells after treatment with DHA. We observed an increase in exosome secretion and exosome microRNA contents from the DHA-treated cells. The expression of 83 microRNAs in the MCF7 exosomes was altered by DHA (>2-fold). The most abundant exosome microRNAs (let-7a, miR-23b, miR-27a/b, miR-21, let-7, and miR-320b) are known to have anti-cancer and/or anti-angiogenic activity. These microRNAs were also increased by DHA treatment in the exosomes from other breast cancer lines (MDA-MB-231, ZR751 and BT20), but not in exosomes from normal breast cells (MCF10A). When DHA-treated MCF7 cells were co-cultured with or their exosomes were directly applied to endothelial cell cultures, we observed an increase in the expression of these microRNAs in the endothelial cells. Furthermore, overexpression of miR-23b and miR-320b in endothelial cells decreased the expression of their pro-angiogenic target genes (PLAU, AMOTL1, NRP1 and ETS2) and significantly inhibited tube formation by endothelial cells, suggesting that the microRNAs transferred by exosomes mediate DHA’s anti-angiogenic action. These effects could be reversed by knockdown of the Rab GTPase, Rab27A, which controls exosome release. Conclusions: We conclude that DHA alters breast cancer exosome secretion and microRNA contents, which leads to the inhibition of angiogenesis. Our data demonstrate that breast cancer exosome signaling can be targeted to inhibit tumor angiogenesis and provide new insight into DHA’s anticancer action, further supporting its use in cancer therapy. Examination of small RNA populations in MCF7 cells and exosomes after DHA treatment.
2015-07-01 | E-GEOD-70432 | 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: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
Project description:Pericardial sac surrounding the heart contains pericardial fluid (PF), which is rich in exosomes. PF exosomes increase angiogenesis in hypoxic endothelial cells and in animal model of hindlimb ischemia by passing the proangiogenic miRNAs to recipient cells. However, under pathological conditions such as diabetes, exosome cargo composition changes and harmful miRNAs can be transferred to the recipient cells and induce more deleterious effects in target tissues. In order to check cargo composition of different PF exosomes, we used PF exosomes from non-diabetic aortic valve replacement (AVR), mitral valve replacement (MVR), coronary artery bypass grafting (CABG) patients and CABG patients with diabetes.
2020-12-31 | GSE118103 | GEO
Project description:MicroRNAs (miRNAs), small (18–22 nucleotides) non-coding RNAs, suppress the translation of target mRNAs by binding to their 3′ untranslated region. Evidence suggests that miRNAs are key regulators of several cellular processes, including angiogenesis. Recent findings indicate that Secreted miRNAs enclosed in exosomes also play an important role in cell–cell communication. To elucidate whether miRNAs secreted from neoplastic cells transfer into endothelial cells and are functionally active in the recipient cells, we investigated the interaction of a leukemia cell line and human umbilical vein endothelial cells (HUVECs).
2012-01-26 | GSE35256 | GEO