Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA170018 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Although Dicer1 functions as a haploinsufficient tumour suppressor its complete loss of function is selected against during tumourigenesis. Here we show that homozygous loss of Dicer1 prevents retinoblastoma formation in mice by synthetic lethality with combined inactivation of the p53 and Rb tumor suppressor pathways. We show that Dicer1 deficiency is tolerated in Rb-deficient retinal progenitor cells harbouring an intact p53 pathway, but not in absence of p53. The synthetic lethal interaction is mediated by the oncogenic miR-17?92 cluster since its deletion phenocopies Dicer1 loss in this context. Accordingly, miR-17?92- inactivation suppresses retinoblastoma formation in mice and co-silencing of miR17/20a and p53 cooperatively decrease the viability of pre-formed human retinoblastoma cells. These data provide important insights into what underlies selective pressure against loss of Dicer1 during tumorigenesis and indicate that targeting Dicer or miR-17-20a family members should be explored as a potential selective therapeutic approach for retinoblastoma prevention and/or treatment. 23 murine samples
2012-07-05 | E-GEOD-39106 | biostudies-arrayexpress
Project description:Although Dicer1 functions as a haploinsufficient tumour suppressor its complete loss of function is selected against during tumourigenesis. Here we show that homozygous loss of Dicer1 prevents retinoblastoma formation in mice by synthetic lethality with combined inactivation of the p53 and Rb tumor suppressor pathways. We show that Dicer1 deficiency is tolerated in Rb-deficient retinal progenitor cells harbouring an intact p53 pathway, but not in absence of p53. The synthetic lethal interaction is mediated by the oncogenic miR-17∼92 cluster since its deletion phenocopies Dicer1 loss in this context. Accordingly, miR-17∼92- inactivation suppresses retinoblastoma formation in mice and co-silencing of miR17/20a and p53 cooperatively decrease the viability of pre-formed human retinoblastoma cells. These data provide important insights into what underlies selective pressure against loss of Dicer1 during tumorigenesis and indicate that targeting Dicer or miR-17-20a family members should be explored as a potential selective therapeutic approach for retinoblastoma prevention and/or treatment. 36 human samples
2012-07-05 | E-GEOD-39105 | biostudies-arrayexpress
Project description:Although Dicer1 functions as a haploinsufficient tumour suppressor its complete loss of function is selected against during tumourigenesis. Here we show that homozygous loss of Dicer1 prevents retinoblastoma formation in mice by synthetic lethality with combined inactivation of the p53 and Rb tumor suppressor pathways. We show that Dicer1 deficiency is tolerated in Rb-deficient retinal progenitor cells harbouring an intact p53 pathway, but not in absence of p53. The synthetic lethal interaction is mediated by the oncogenic miR-17∼92 cluster since its deletion phenocopies Dicer1 loss in this context. Accordingly, miR-17∼92- inactivation suppresses retinoblastoma formation in mice and co-silencing of miR17/20a and p53 cooperatively decrease the viability of pre-formed human retinoblastoma cells. These data provide important insights into what underlies selective pressure against loss of Dicer1 during tumorigenesis and indicate that targeting Dicer or miR-17-20a family members should be explored as a potential selective therapeutic approach for retinoblastoma prevention and/or treatment.
2012-07-05 | GSE39106 | GEO
Project description:Although Dicer1 functions as a haploinsufficient tumour suppressor its complete loss of function is selected against during tumourigenesis. Here we show that homozygous loss of Dicer1 prevents retinoblastoma formation in mice by synthetic lethality with combined inactivation of the p53 and Rb tumor suppressor pathways. We show that Dicer1 deficiency is tolerated in Rb-deficient retinal progenitor cells harbouring an intact p53 pathway, but not in absence of p53. The synthetic lethal interaction is mediated by the oncogenic miR-17∼92 cluster since its deletion phenocopies Dicer1 loss in this context. Accordingly, miR-17∼92- inactivation suppresses retinoblastoma formation in mice and co-silencing of miR17/20a and p53 cooperatively decrease the viability of pre-formed human retinoblastoma cells. These data provide important insights into what underlies selective pressure against loss of Dicer1 during tumorigenesis and indicate that targeting Dicer or miR-17-20a family members should be explored as a potential selective therapeutic approach for retinoblastoma prevention and/or treatment.
2012-07-05 | GSE39105 | GEO
Project description:Synthetic lethality between Rb, p53 and miR-17~92 in retinal progenitors suppresses retinoblastoma formation_murine data
| PRJNA170019 | ENA
Project description:Mouse retinal samples were collected at postnatal day 8 (P8). Each contain different perturbations in retinoblastoma (RB) gene function in order to evaluate the dependency of CDK2 on the RB-E2F axis.
2017-09-01 | GSE86372 | GEO
Project description:The p53 family comprises the tumor suppressor p53 and the structural homologs p63 and p73. How the three family members cooperate in tumor suppression remains unclear. Here, we report different but complementary functions of the individual members for regulating retinoblastoma protein (RB) function during myogenic differentiation. Whereas p53 transactivates the retinoblastoma gene, p63 and p73 induce the cyclin-dependent kinase inhibitor p57 to maintain RB in an active, hypophosphorylated state. DeltaNp73 inhibits these functions of the p53 family in differentiation control, prevents myogenic differentiation, and enables cooperating oncogenes to transform myoblasts to tumorigenicity. DeltaNp73 is frequently overexpressed in rhabdomyosarcoma and essential for tumor progression in vivo. These findings establish differentiation control as a key tumor suppressor activity of the p53 family. Experiment Overall Design: DeltaNp73 alpha expressing C2C12 myoblasts examined 6 and 24 hours after shifting the cells to a differentiation medium.
2007-11-22 | E-GEOD-5447 | biostudies-arrayexpress
Project description:Emerging evidence has shown that noncoding RNAs, particularly microRNAs (miRNAs), contribute to the pathogenesis of mood and anxiety disorders, although the molecular mechanisms are poorly understood. Here we show altered levels of miR-17-92 in adult hippocampal neural progenitors have a significant impact in neurogenesis and anxiety- and depression-related behaviors in mice. miR-17-92 deletion in adult neural progenitors causes a decrease, while its overexpression an increase of neurogenesis in the dentate gyrus, through regulating genes in the glucocorticoid pathway, especially serum- and glucocorticoid-inducible protein kinase-1 (Sgk1). miR-17-92 knockout mice show anxiety- and depression-like behaviors, whereas miR-17-92 overexpressing mice exhibit anxiolytic and antidepression-like behaviors. Furthermore, we show that miR-17-92 expression in the adult mouse hippocampus responds to chronic stress, and miR-17-92 rescues proliferation defects, induced by corticosterone, in hippocampal neural progenitors. Our study uncovers a crucial role for miR-17-92 in adult neural progenitors to regulate neurogenesis and anxiety- and depression-like behaviors.
2016-12-09 | GSE83636 | GEO
Project description:Retinoblastoma is a childhood retinal tumor that initiates in response to biallelic RB1 inactivation. We show that post-mitotic human cone precursors are uniquely sensitive to the oncogenic effects of Rb depletion. Rb knockdown induced cone precursor proliferation in prospectively isolated populations. SNP-array analysis of two Rb/p130-depleted cone precursor cell lines, revealing no megabase-size loss of heterozygosity (LOH) or copy number alterations (CNAs). SNP-array analysis of one Rb/p130-depleted (tumor 1) or one Rb-depleted (tumor 2) cone precursor-derived tumors, revealing no megabase-size LOH or CNAs, consistent with the lack of DNA copy number alterations in some retinoblastomas. Thus, the cone precursor tumors resembled human retinoblastomas at the molecular cytogenetic level. High resolution SNP-array DNA copy number analyses were performed using CytoScan® HD (Affymetrix, 901835) according to the manufacturer's directions. Data were analyzed using Chromosome Analysis Suite 2.0 (Affymetrix). DNA was extracted from two Rb/p130 depleted cone precursor cell lines and two cryopreserved mouse retinoblastoma samples from eyes xenograted with Rb/p130 or Rb depleted cone precursors. Affymetrix SNP analysis on retinoblastoma cell lines Y79, RB176, and WERI were used as control. Normal human genome 19 was used as reference.
2014-08-25 | E-GEOD-60720 | biostudies-arrayexpress