Homo sapiens
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: E-GEOD-20745
PROVIDER: PRJNA124989 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:MicroRNAs are endogenously expressed small non-coding RNAs that regulate gene expression on the posttranscriptional level. The miR-17-92 cluster (encoding miR-17, -18a, -19a/b, -20a and miR-92a) is highly expressed in tumor cells and is up-regulated by ischemia. Whereas miR-92a was recently identified as negative regulator of angiogenesis, the specific functions of the other members of the cluster are less clear. Here we demonstrate that overexpression of miR-17, -18a, -19a and -20a significantly inhibited 3D spheroid sprouting in vitro, whereas inhibition of miR-17, -18a and -20a augmented endothelial cell (EC) sprout formation. Inhibition of miR-17 and miR-20a in vivo using antagomirs significantly increased the number of perfused vessels in matrigel plugs, whereas antagomirs, that specifically target miR-18a and miR-19a were less effective. However, systemic inhibition of miR-17/20 did not affect tumor angiogenesis. Further mechanistic studies showed that miR-17/20 targets several pro-angiogenic genes. Specifically, Janus kinase 1 (Jak1) was shown to be a direct target of miR-17. In summary, we show that miR-17/20 exhibit a cell intrinsic anti-angiogenic activity in ECs. Inhibition of miR-17/20 specifically augmented neovascularization of matrigel plugs, but did not affect tumor angiogenesis indicating a context-dependent regulation of angiogenesis by miR-17/20 in vivo. 6 samples of 3 independent experiments (n=3): per experiment Pre-miR-Co (10 nM, Ambion) and Pre-miR-17 (10 nM, Ambion) transfected HUVEC 24h after transfection
2010-03-23 | E-GEOD-20745 | biostudies-arrayexpress
Project description:MicroRNAs are endogenously expressed small non-coding RNAs that regulate gene expression on the posttranscriptional level. The miR-17-92 cluster (encoding miR-17, -18a, -19a/b, -20a and miR-92a) is highly expressed in tumor cells and is up-regulated by ischemia. Whereas miR-92a was recently identified as negative regulator of angiogenesis, the specific functions of the other members of the cluster are less clear. Here we demonstrate that overexpression of miR-17, -18a, -19a and -20a significantly inhibited 3D spheroid sprouting in vitro, whereas inhibition of miR-17, -18a and -20a augmented endothelial cell (EC) sprout formation. Inhibition of miR-17 and miR-20a in vivo using antagomirs significantly increased the number of perfused vessels in matrigel plugs, whereas antagomirs, that specifically target miR-18a and miR-19a were less effective. However, systemic inhibition of miR-17/20 did not affect tumor angiogenesis. Further mechanistic studies showed that miR-17/20 targets several pro-angiogenic genes. Specifically, Janus kinase 1 (Jak1) was shown to be a direct target of miR-17. In summary, we show that miR-17/20 exhibit a cell intrinsic anti-angiogenic activity in ECs. Inhibition of miR-17/20 specifically augmented neovascularization of matrigel plugs, but did not affect tumor angiogenesis indicating a context-dependent regulation of angiogenesis by miR-17/20 in vivo.
2010-03-13 | GSE20745 | GEO
Project description:MycRas vs Ras colon carcinoma. Human adenocarcinomas commonly harbor mutations in the Ki-Ras and c-Myc proto-oncogenes and the trp53 tumor suppressor gene. All three genetic lesions are potentially pro-angiogenic, since they sustain production of the vascular endothelial growth factor (VEGF). Yet murine Ki-Ras/p53-null colonocytes formed indolent, poorly vascularized tumors, whereas additional transduction with a Myc-encoding retrovirus promoted vigorous vascularization and growth. While VEGF levels were unaffected by Myc, enhanced neovascularization correlated with down-regulation of anti-angiogenic thrombospondin-1 (Tsp1) and related proteins, such as connective tissue growth factor (CTGF). Both Tsp1 and CTGF are predicted targets for repression by the miR-17-92 microRNA cluster, which was upregulated in RasMyc colonocytes. Indeed, miR-17-92 knock-down with antisense 2’-O-methyl oligoribonucleotides partly restored Tsp1 and CTGF expression, and conversely, transduction of Ras-only cells with a miR-17-92-encoding retrovirus reduced Tsp1 and CTGF levels. Importantly, miR-17-92-transduced cells formed larger, better perfused tumors. These findings establish a role for microRNAs in non-cell-autonomous Myc-induced tumor phenotypes.
2006-09-08 | E-MEXP-757 | biostudies-arrayexpress
Project description:Knockout of the ubiquitously expressed microRNA-17~92 cluster in mice produces a lethal developmental lung defect. We validated the equally widely expressed pro-apoptotic Bim gene as joint target of miR-17~92 cluster members. To study the contribution of miR-17~92:Bim interaction to miR-17~92 overall function, we set up a system of conditional mutagenesis of the Bim 3’UTR. Blocking miR-17~92:Bim interaction early in development phenocopied the lethal lung phenotype of miR-17~92 ablation. Thus, despite hundreds of overall predicted targets vital miRNA functions can be mediated by a single target gene.
2019-11-10 | GSE123671 | GEO
Project description:Objective: To characterize downstream effectors of p300 acetyltransferase in the myocardium. Background: Acetyltransferase p300 is a central driver of the hypertrophic response to increased workload, but its biological targets and downstream effectors are incompletely known. Methods and Results: Mice expressing a myocyte-restricted transgene encoding acetyltransferase p300, previously shown to develop spontaneous hypertrophy, were observed to undergo robust compensatory blood vessel growth together with increased angiogenic gene expression. Chromatin immunoprecipitation demonstrated binding of p300 to the enhancers of the angiogenic regulators Angpt1 and Egln3. Interestingly, p300 overexpression in vivo was also associated with relative upregulation of several members of the anti-angiogenic miR-17~92 cluster in vivo. Confirming this finding, both miR-17-3p and miR-20a were upregulated in neonatal rat ventricular myocytes following adenoviral transduction of p300. Relative expression of most members of the 17~92 cluster was similar in all 4 cardiac chambers and in other organs, however, significant downregulation of miR-17-3p and miR-20a occurred between 1 and 8 months of age in both wt and tg mice. The decline in expression of these microRNAs was associated with increased expression of VEGFA, a validated miR-20a target. In addition, miR-20a was demonstrated to directly repress p300 expression through a consensus binding site in the p300 3’UTR. In vivo transduction of p300 resulted in repression both of p300 and of p300-induced angiogenic transcripts. Conclusion: p300 drives an angiogenic transcription program during hypertrophy that is fine-tuned in part through direct repression of p300 by miR-20a. 4 littermates, 3 transgene-expressing and 1 wild-type were analyzed. Samples were spotted in duplicate.
2013-09-30 | E-GEOD-50843 | biostudies-arrayexpress
Project description:Objective: To characterize downstream effectors of p300 acetyltransferase in the myocardium. Background: Acetyltransferase p300 is a central driver of the hypertrophic response to increased workload, but its biological targets and downstream effectors are incompletely known. Methods and Results: Mice expressing a myocyte-restricted transgene encoding acetyltransferase p300, previously shown to develop spontaneous hypertrophy, were observed to undergo robust compensatory blood vessel growth together with increased angiogenic gene expression. Chromatin immunoprecipitation demonstrated binding of p300 to the enhancers of the angiogenic regulators Angpt1 and Egln3. Interestingly, p300 overexpression in vivo was also associated with relative upregulation of several members of the anti-angiogenic miR-17~92 cluster in vivo. Confirming this finding, both miR-17-3p and miR-20a were upregulated in neonatal rat ventricular myocytes following adenoviral transduction of p300. Relative expression of most members of the 17~92 cluster was similar in all 4 cardiac chambers and in other organs, however, significant downregulation of miR-17-3p and miR-20a occurred between 1 and 8 months of age in both wt and tg mice. The decline in expression of these microRNAs was associated with increased expression of VEGFA, a validated miR-20a target. In addition, miR-20a was demonstrated to directly repress p300 expression through a consensus binding site in the p300 3’UTR. In vivo transduction of p300 resulted in repression both of p300 and of p300-induced angiogenic transcripts. Conclusion: p300 drives an angiogenic transcription program during hypertrophy that is fine-tuned in part through direct repression of p300 by miR-20a.
2013-09-30 | GSE50843 | GEO
Project description:Knockout of the ubiquitously expressed microRNA-17~92 cluster in mice produces a lethal developmental defect and blocked B lymphopoiesis. We validated the equally widely expressed Bcl2l11 gene as joint target of miR-17~92 cluster members. Bcl2l11 encodes the pro-apoptotic protein BIM, central to life-death decisions in most mammalian cells. To study the contribution of miR-17~92:Bim interaction to miR-17~92 overall function, we set up a system of conditional mutagenesis of the Bim 3’UTR in the mouse. Blocking miR-17~92:Bim interaction early in development phenocopied the lethal developmental defect of miR-17~92 ablation. In contrast, hematopoietic and B lineage specific mutagenesis, while selectively compromising B lineage cell fitness, left hematopoietic cell compartments untouched as long as the cells expressed Bim biallelically. Thus, despite hundreds of overall predicted targets vital miRNA functions can be mediated by a single target gene, depending on cellular context and level of target gene expression.
2019-11-13 | GSE123672 | GEO
Project description:A network of gene regulatory factors such as transcription factors and microRNAs establish and maintain the gene expression pattern during hematopoiesis. In this network transcription factors regulate each other and are involved in regulatory loops with microRNAs.The microRNA cluster miR-17-92 is located within the MIR17HG gene and encodes for six mature microRNAs. It is important for hematopoietic differentiation and plays a central role in malignant disease. However, the transcription factors downstream of miR-17-92 are largely elusive and the transcriptional regulation of miR-17-92 is not fully understood. Here we show that miR-17-92 forms a regulatory loop with the transcription factor TAL1. The miR-17-92 cluster inhibits expression of TAL1 and indirectly leads to decreased stability of the TAL1 transcriptional complex. We found that TAL1 and its heterodimerization partner E47 regulate miR-17-92 transcriptionally. Furthermore, miR-17-92 negatively influences erythroid differentiation, a process that depends on gene activation by the TAL1 complex. Our data give example of how transcription factor activity is fine-tuned during normal hematopoiesis. We postulate that disturbance of the regulatory loop between TAL1 and the miR-17-92 cluster could be an important step in cancer development and progression.
2021-09-09 | PXD018052 | Pride
Project description:The miR-17-92 microRNA cluster is often activated in cancer cells, but the identity of its targets remains largely elusive. Here we examined the effects of activation of the entire miR-17-92 cluster on global protein expression in neuroblastoma cells. In this dataset we deposit global mRNA expression data obtained form primary neuroblastoma tumour cells. This data was used to demonstrate negative correlation between TGFB target gene expression and expression of the miR-17-92 cluster.
2010-12-01 | GSE21713 | GEO
Project description:The miR-17-92 cluster targets mRNAs involved in distinct pathways which either promote or inhibit tumor progression. However, the cellular and molecular mechanisms underlying miR-17~92 cluster mediated pro- or anti- tumorigenic effects has not been studied. In this study, we found that inhibition of colon cancer progression is dictated by quantitatively controlling expression of the miR-17~92 cluster. To identify molecular mechanisms giving rise to the different growth/metastasis patterns, we profiled gene expression in miR-Ctrl, miR-17~92Med and miR-17~92Hi cells using Affymetrix Murine GeneST Arrays.
2014-06-01 | GSE55631 | GEO