Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA275789 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR1810470.fastq.gz | Fastqsanger.gz | |||
| SRR1810480.fastq.gz | Fastqsanger.gz | |||
| SRR1810490.fastq.gz | Fastqsanger.gz | |||
| SRR1810471.fastq.gz | Fastqsanger.gz | |||
| SRR1810481.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 22 |
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Project description:MicroRNA-203 represses selection and expansion of oncogenic HRas transformed tumor initiating cells
| PRJNA275785 | ENA
Project description:MicroRNA-203 represses selection and expansion of oncogenic HRas transformed tumor initiating cells [array]
| PRJNA275787 | ENA
Project description:In many mouse models of skin cancer, only a few tumors typically form although many cells competent for tumorigenesis receive the same oncogenic mutations. These observations suggest a selection process for defining tumor initiating cells. Here we use quantitative mRNA- and miR-Seq to determine the impact of HRasG12V on the transcriptome of keratinocytes. We discover that microRNA-203 is downregulated by HRasG12V. Using a knockout mouse model, we demonstrate that loss of microRNA-203 promotes selection and expansion of tumor-initiating cells. Conversely, restoration of microRNA-203 with an inducible model potently inhibits proliferation of these cells. We comprehensively identify microRNA-203 targets required for HRas-initiated tumorigenesis. These targets include important effectors of the Ras pathway and essential genes required for cell division. Together, this study establishes a role for the loss of microRNA-203 in promoting selection and expansion of HRas mutated cells and identifies a mechanism through which microRNA-203 antagonizes HRas-mediated tumorigenesis. Identifying mRNA and microRNA networks regulated by oncogenic HRasG12V in primary keratinocytes through the use of 3Seq and small-RNA-Sequencing. Additionally we utilize ribosome-profiling, 3Seq, Microarray and Ago2-HITS-CLIP approaches to identify novel miR-203 target genes.
2015-07-23 | E-GEOD-66054 | biostudies-arrayexpress
Project description:In many mouse models of skin cancer, only a few tumors typically form although many cells competent for tumorigenesis receive the same oncogenic mutations. These observations suggest a selection process for defining tumor initiating cells. Here we use quantitative mRNA- and miR-Seq to determine the impact of HRasG12V on the transcriptome of keratinocytes. We discover that microRNA-203 is downregulated by HRasG12V. Using a knockout mouse model, we demonstrate that loss of microRNA-203 promotes selection and expansion of tumor-initiating cells. Conversely, restoration of microRNA-203 with an inducible model potently inhibits proliferation of these cells. We comprehensively identify microRNA-203 targets required for HRas-initiated tumorigenesis. These targets include important effectors of the Ras pathway and essential genes required for cell division. Together, this study establishes a role for the loss of microRNA-203 in promoting selection and expansion of HRas mutated cells and identifies a mechanism through which microRNA-203 antagonizes HRas-mediated tumorigenesis. Identifying mRNA and microRNA networks regulated by oncogenic HRasG12V in primary keratinocytes through the use of 3Seq and small-RNA-Sequencing. Additionally we utilize ribosome-profiling, 3Seq, Microarray and Ago2-HITS-CLIP approaches to identify novel miR-203 target genes.
2015-07-23 | E-GEOD-66055 | biostudies-arrayexpress
Project description:In many mouse models of skin cancer, only a few tumors typically form although many cells competent for tumorigenesis receive the same oncogenic mutations. These observations suggest a selection process for defining tumor initiating cells. Here we use quantitative mRNA- and miR-Seq to determine the impact of HRasG12V on the transcriptome of keratinocytes. We discover that microRNA-203 is downregulated by HRasG12V. Using a knockout mouse model, we demonstrate that loss of microRNA-203 promotes selection and expansion of tumor-initiating cells. Conversely, restoration of microRNA-203 with an inducible model potently inhibits proliferation of these cells. We comprehensively identify microRNA-203 targets required for HRas-initiated tumorigenesis. These targets include important effectors of the Ras pathway and essential genes required for cell division. Together, this study establishes a role for the loss of microRNA-203 in promoting selection and expansion of HRas mutated cells and identifies a mechanism through which microRNA-203 antagonizes HRas-mediated tumorigenesis.
2015-07-23 | GSE66055 | GEO
Project description:In many mouse models of skin cancer, only a few tumors typically form although many cells competent for tumorigenesis receive the same oncogenic mutations. These observations suggest a selection process for defining tumor initiating cells. Here we use quantitative mRNA- and miR-Seq to determine the impact of HRasG12V on the transcriptome of keratinocytes. We discover that microRNA-203 is downregulated by HRasG12V. Using a knockout mouse model, we demonstrate that loss of microRNA-203 promotes selection and expansion of tumor-initiating cells. Conversely, restoration of microRNA-203 with an inducible model potently inhibits proliferation of these cells. We comprehensively identify microRNA-203 targets required for HRas-initiated tumorigenesis. These targets include important effectors of the Ras pathway and essential genes required for cell division. Together, this study establishes a role for the loss of microRNA-203 in promoting selection and expansion of HRas mutated cells and identifies a mechanism through which microRNA-203 antagonizes HRas-mediated tumorigenesis.
2015-07-23 | GSE66054 | GEO
Project description:Silencing of gene expression by methylation of CpG islands in regulatory elements is frequently observed in cancer. However, an influence of the most common oncogenic signalling pathways onto DNA methylation has not yet been investigated thoroughly. To address this issue, we identified genes suppressed in HRAS-transformed rat fibroblasts but up-regulated after treatment with the demethylating agent 5-Aza-CdR and with the MEK1,2 inhibitor U0126. Analysis of gene expression by microarray and Northern blot analysis revealed the MEK/ERK target genes clusterin, Mmp2, Ppicap, syndecan 4, Timp2, Thbs1 to be repressed in the HRAS-transformed FE-8 cells in a MEK/ERK- and in a methylation-dependent manner. Hypermethylation of putative regulatory elements in HRAS-transformed cells as compared to immortalized fibroblasts was detected within a CpG island 14.5 kb upstream of clusterin, within the clusterin promoter and within a CpG island of the Mmp2 promoter by bisulphite sequencing. Furthermore, hypermethylation of the clusterin promoter was observed ten days after induction of HRAS in immortalized rat fibroblasts and a clear correlation between reduced clusterin expression and hypermethlyation could also be observed in distinct rat tissues. These results suggest that silencing of individual genes by DNA methylation is controlled by oncogenic signalling pathways, yet the mechanisms responsible for initial target gene suppression are variable. Experiment Overall Design: Gene expression was analyzed in immortal (208F) and HRAS oncogene-transformed (FE8) rat fibroblasts after demethylation by 5-aza-2'-deoxycytidine. Genes potentially methylated in RAS-transformed cells were identified by bisulphite sequencing
2007-11-06 | E-GEOD-4427 | biostudies-arrayexpress
Project description:Silencing of gene expression by methylation of CpG islands in regulatory elements is frequently observed in cancer. However, an influence of the most common oncogenic signalling pathways onto DNA methylation has not yet been investigated thoroughly. To address this issue, we identified genes suppressed in HRAS-transformed rat fibroblasts but up-regulated after treatment with the demethylating agent 5-Aza-CdR and with the MEK1,2 inhibitor U0126. Analysis of gene expression by microarray and Northern blot analysis revealed the MEK/ERK target genes clusterin, Mmp2, Ppicap, syndecan 4, Timp2, Thbs1 to be repressed in the HRAS-transformed FE-8 cells in a MEK/ERK- and in a methylation-dependent manner. Hypermethylation of putative regulatory elements in HRAS-transformed cells as compared to immortalized fibroblasts was detected within a CpG island 14.5 kb upstream of clusterin, within the clusterin promoter and within a CpG island of the Mmp2 promoter by bisulphite sequencing. Furthermore, hypermethylation of the clusterin promoter was observed ten days after induction of HRAS in immortalized rat fibroblasts and a clear correlation between reduced clusterin expression and hypermethlyation could also be observed in distinct rat tissues. These results suggest that silencing of individual genes by DNA methylation is controlled by oncogenic signalling pathways, yet the mechanisms responsible for initial target gene suppression are variable. Keywords: expression analysis
2006-03-12 | GSE4427 | GEO
Project description:Oncogenic transformation of individual cell fates by developmental signaling cascades and transcription factors triggers diverse cancer types. Chordoma is a rare, aggressive tumor arising from transformed notochord remnants. Various potentially oncogenic factors have been found deregulated in chordoma and its metastases, yet clear causation remains uncertain. In particular, expression of the notochord-controlling transcription factor Brachyury is hypothesized as key molecular driver in chordoma formation, yet an in vivo model to causally test its oncogenic potential in the notochord is missing. Here, we apply a zebrafish model of chordoma onset to identify the notochord-transforming potential of tumor-implicated candidate genes in vivo. We find that overexpression of human and zebrafish Brachyury, including a version with augmented transcriptional activity, is insufficient to initiate notochord hyperplasia in vivo. In contrast, the repeatedly chordoma-implicated receptor tyrosine kinase (RTK) genes EGFR and KDR/VEGFR2 are sufficient to transform developmental notochord cells, akin to direct activation of Ras. Analysis of transcriptome and sub-cellular organization from transformed notochords suggests that aberrant activation of RTK/Ras signaling attenuates processes required for the differentiation of notochord cells. Taken together, our results provide first in vivo indication for a lack of tumor-initiating potential of Brachyury expression in the notochord, and suggest activated RTK signaling as potent hyperplasia-initiating event in chordoma.
2018-12-01 | E-MTAB-7349 | biostudies-arrayexpress
Project description:Maintaining a full differentiation potential along self-renewal ability is a major property of stem cells during development and regeneration. miR-203 is a microRNA previously involved in skin differentiation and tumor suppression. We show here that transient expression of miR-203 enhances the potential of embryonic (ESC) and induced pluripotent stem cells (iPSC) in contributing to multiple lineages without decreasing their self-renewal properties. In fact, miR-203 significantly improves the efficiency of ES/iPS cells in the generation of quimeras and tetraploid complementation assays, in addition to improving the generation of complex teratomas and embryo-like structures in vivo. These effects are mediated by the direct miR-203-dependent repression of de novo DNA methyltransferases Dnmt3a and Dnmt3b, leading to genome-wide demethylation of pluripotent cells. Transient exposure to miR-203 improves functional differentiation and maturation of pluripotent cells into cardiomyocytes in a Dnmt3a/b-dependent manner, suggesting the possible therapeutic uses of this microRNA in regenerative medicine.
2020-07-05 | GSE86899 | GEO