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Elevating Sox2 levels deleteriously affects the growth of glioblastoma and medulloblastoma cells.

ABSTRACT: Induction of the transcription factor Sox2 from a doxycycline-inducible promoter in iSox2-DAOY medulloblastoma cells. Affymetrix microarrays were used to characterize the gene expression profile of iSox2-DAOY cells in the absence and presence of doxycycline.

ORGANISM(S): Homo sapiens

PROVIDER: GSE36947 | GEO | 2012/08/25

SECONDARY ACCESSION(S): PRJNA157109

REPOSITORIES: GEO

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Elevating Sox2 levels deleteriously affects the growth of glioblastoma and medulloblastoma cells.

Project description:Induction of the transcription factor Sox2 from a doxycycline-inducible promoter in iSox2-DAOY medulloblastoma cells. Affymetrix microarrays were used to characterize the gene expression profile of iSox2-DAOY cells in the absence and presence of doxycycline. Human DAOY medulloblastoma cells were engineered to express epitope tagged Sox2 under the control of a doxycycline inducible promoter, to produce iSox2-DAOY cells. iSox2-DAOY cells were FACS sorted into CD133 low and high populations. The CD133 low population was cultured in the absence and presence of 0.5 Âµg/mL doxycycline for 24 hours. RNA was extracted from cells cultured without and with doxycycline, and was used for microarray analysis.

2012-08-25 | E-GEOD-36947 | biostudies-arrayexpress

Elevating Sox2 levels deleteriously affects the growth of glioblastoma and medulloblastoma cells

Project description: Not available

| S-ECPF-GEOD-36947 | biostudies-other

Elevating SOX2 levels deleteriously affects the growth of medulloblastoma and glioblastoma cells.

Project description: Not available

| S-EPMC3429438 | biostudies-literature

VAPB regulates proliferation in medulloblastoma

Project description:RNA sequencing of medulloblastoma cell lines DAOY and USP13-med; wild type and VAPB KO.

2023-06-28 | E-MTAB-11914 | biostudies-arrayexpress

Gene expression profiling of Sox2+ Patched1+/- medulloblastoma cells

Project description:Only a minority of medulloblastoma cells can self-renew and sustain tumor growth. In the Patched1+/- mouse model, these cells are quiescent and express the stem cell marker Sox2. We sought to define the gene expression profiling of these cells to gain insight into the molecular pathways that govern this population. Sox2-expressing and Sox2-negative cells were isolated from primary Sox2-eGFP;Patched1+/- tumors as GFP+ or GFP- tumors, respectively.

2016-07-08 | GSE48766 | GEO

LC-MS/MS analysis of Daoy and UW228 medulloblastoma cell lines

Project description:The goal of this study was to profile the total proteome and transcriptome of the established medulloblastoma cell lines, Daoy and UW228, using label-free nano-LC-MS/MS-based quantitative proteomics and high-throughput RNA sequencing (RNA-Seq), coupled with pathway analysis to identify differentially expressed genes, proteins and signaling pathways with potential as prognostic markers. A total of 14250 and 12870 transcripts were detected for Daoy and UW228, respectively. Proteomic profiling identified 2630 and 1235 proteins in Daoy and UW228, representing 18% and 10% of detected transcripts, respectively. Interestingly, Daoy proteome included >50% unique proteins, while almost 90% of proteins expressed by UW228 were commonly expressed in Daoy. Differential expression of a number of adhesion, cytoskeletal and signaling molecules were observed between the two cell lines. Upregulation of a number of proteins and enrichment of key signaling pathways, including WNT, Sonic hedgehog (SHH) and integrin signaling pathways, were uniquely observed in MB cell lines, in particular in Daoy.

2017-10-27 | PXD002659 | Pride

Elevating SOX2 downregulates MYC through a SOX2:MYC signaling axis and induces a slowly cycling proliferative state in human tumor cells

Project description:Quiescent/slowly circling tumor cells present a clinical challenge due to their ability to evade treatement. Recent studies have demonstrated that quiescent/slow circling tumor cells hijack embryonic growth arrest mechanisms and consequently resist chemotherapy. Significantly, earlier studies established that high levels of SOX2 in both fetal and tumor cells restrict cell proliferation and induce a slowly cycling state. However, the mechanisms through which elevated SOX2 levels inhibit tumor cell proliferation have not been identified. To identify common mechanisms through which SOX2 elevation restricts tumor cell proliferation, we performed RNA-seq using ONS76 medulloblastoma and LNCaP prostate tumor cells engineered to express SOX2 from an inducible promoter. SOX2 elevation in both cell lines significantly downregulated MYC target genes. Consistent with these findings, elevating SOX2 in five cell lines representing three different human cancer types decreases MYC mRNA and protein levels. Importantly, the expression of a dominant-negative MYC variant, omomyc, recapitulated many of the effects of SOX2 on proliferation, cell cycle, and gene expression. As predicted by our Gene Ontology analysis, elevating SOX2 decreases biosynthetic activity, in particular protein translation. We also demonstrate that rescuing MYC activity in the context of elevated SOX2 induces cell death, indicating that the downregulation of MYC is a critical mechanistic step necessary to maintain survival in the slowly cycling state induced by elevated SOX2. Altogether, our findings uncover a novel SOX2: MYC signaling axis and provide novel insights into the molecular mechanisms through which SOX2 elevation induces a slowly cycling proliferative state.

2022-08-03 | GSE190936 | GEO

Downregulation of ARID1B, a tumor-suppressor in the WNT subgroup medulloblastoma, activates multiple oncogenic signaling pathways

Project description:About 85% of WNT subgroup medulloblastomas exhibit the loss of one copy of chromosome 6. Loss of function mutations were identified in the ARID1B gene located on chromosome 6 in WNT subgroup tumors suggesting tumor suppressor role for ARID1B in WNT medulloblastomas. The expression of ARID1B was downregulated in the medulloblastoma cell line Daoy using two independent shRNA sequences in a doxycycline-inducible lentiviral vector tet-pLKO-puro and the effect of its downregulation on the gene expression profile was studied by the RNA-seq analysis

2021-08-26 | GSE163810 | GEO

Sox2 levels configure the WNT response of epiblast progenitors responsible for vertebrate body formation. [EXP1_ATACSeq]

Project description:In this experiment the relationship between SOX2 levels and chromatin accessibility was assayed using ATAC-seq during embryonic stem cell differentiation. A doxycycline inducible cell line (SOX2 TetON) was employed to experimentally control SOX2 expression.

2021-12-31 | GSE162762 | GEO

Medulloblastoma associated DDX3X mutants restore malignant potential of medulloblastoma cells decreased upon the loss of DDX3X expression

Project description:DDX3X is an ATP-dependent RNA helicase. Missense mutations in DDX3X gene are known to occur in WNT, SHH subgroup medulloblastomas. The role of DDX3X in medulloblastoma biology was studied by downregulating its expression in a SHH subgroup Daoy medulloblastoma cell line. DDX3X knockdown resulted in considerable reduction in proliferation, clonogenic potential and anchorage-independent growth of the medulloblastoma cells. Transcriptome analysis was performed to delineate the molecular mechanism underlying reduction in the malignant potential of the medulloblastoma cells upon DDX3X knockdown. Exogenous expression of three DDX3X missense mutants in the DDX3X knockdown cells could restore the malignant potential of the medulloblastoma cells.

2023-03-31 | GSE201967 | GEO

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