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Epigenetic regulation of metabolic adaptation predicts response to Inositol hexakisphosphate (IP6) treatment in Group 4 medulloblastoma

ABSTRACT: Epigenetic regulation of metabolic adaptation predicts response to Inositol hexakisphosphate (IP6) treatment in Group 4 medulloblastoma

PROVIDER: PRJNA656704 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12215700_1.fastq.gz	Fastqsanger.gz
	SRR12215700_2.fastq.gz	Fastqsanger.gz
	SRR12215800_1.fastq.gz	Fastqsanger.gz
	SRR12215800_2.fastq.gz	Fastqsanger.gz
	SRR12215701_1.fastq.gz	Fastqsanger.gz

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Epigenetic regulation of metabolic adaptation predicts response to Inositol hexakisphosphate (IP6) treatment in Group 4 medulloblastoma (HumanMethylation850)

Project description:Deregulation of chromatin modifiers plays an essential role in the pathogenesis of medulloblastoma (MB), the most common paediatric malignant brain tumour. Here, we identify a BMI1-dependent sensitivity to deregulation of inositol metabolism in a proportion of medulloblastoma. We demonstrate mTOR pathway activation and metabolic adaptation specifically in medulloblastoma of the molecular subgroup G4 characterised by a BMI1High;CHD7Low signature and show this can be counteracted by IP6 treatment. Finally, we demonstrate that IP6 synergises with cisplatin to enhance its cytotoxicity in vitro and extends survival in a pre-clinical BMI1High;CHD7Low xenograft model.

2021-03-04 | GSE155962 | GEO

Epigenetic regulation of metabolic adaptation predicts response to Inositol hexakisphosphate (IP6) treatment in Group 4 medulloblastoma (RNA-seq, ChIP-seq)

2021-03-04 | GSE154394 | GEO

Epigenetic regulation of metabolic adaptation predicts response to Inositol hexakisphosphate (IP6) treatment in Group 4 medulloblastoma (HumanMethylation850)

Project description:Epigenetic regulation of metabolic adaptation predicts response to Inositol hexakisphosphate (IP6) treatment in Group 4 medulloblastoma (HumanMethylation850)

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Epigenetic regulation of metabolic adaptation predicts response to Inositol hexakisphosphate (IP6) treatment in Group 4 medulloblastoma (RNA-seq, ChIP-seq)

Project description:Epigenetic regulation of metabolic adaptation predicts response to Inositol hexakisphosphate (IP6) treatment in Group 4 medulloblastoma (RNA-seq, ChIP-seq)

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Epigenetic regulation of metabolic adaptation predicts response to Inositol hexakisphosphate (IP6) treatment in Group 4 medulloblastoma

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-03-04 | GSE156077 | GEO

Inositol treatment inhibits medulloblastoma through suppression of epigenetic-driven metabolic adaptation.

Project description:Deregulation of chromatin modifiers plays an essential role in the pathogenesis of medulloblastoma, the most common paediatric malignant brain tumour. Here, we identify a BMI1-dependent sensitivity to deregulation of inositol metabolism in a proportion of medulloblastoma. We demonstrate mTOR pathway activation and metabolic adaptation specifically in medulloblastoma of the molecular subgroup G4 characterised by a BMI1High;CHD7Low signature and show this can be counteracted by IP6 treatment. Finally, we demonstrate that IP6 synergises with cisplatin to enhance its cytotoxicity in vitro and extends survival in a pre-clinical BMI1High;CHD7Low xenograft model.

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Inositol signaling in the basidiomycete fungus Schizophyllum commune

Project description:Intracellular signaling is conserved in eukaryotes to allow for response to extracellular signals and to regulate development and cellular functions. In fungi, inositol phosphate signaling has been shown to be involved in growth, sexual reproduction, and metabolic adaptation lacking, however, reports of mushroom forming fungi so far. In Schizophyllum commune, an inositol monophosphatase has been found up-regulated during sexual development. The enzyme is crucial for inositol cycling where it catalyzes the last step of inositol phosphate metabolism restoring the inositol pool from the monophosphorylated inositol monophosphate. We overexpressed the gene in this model basidiomycete and verified its involvement in cell wall integrity and intracellular trafficking. Strong phenotypes in mushroom formation and cell metabolism were evidenced by proteome analyses. In addition, altered inositol signaling was shown to be involved in tolerance towards cesium and zinc, and increased metal tolerance towards cadmium, associated with induced expression of kinases and repression of phosphatases within the inositol cycle. The presence of the heavy metals Sr, Cs, Cd, and Zn lowered intracellular calcium levels. We could develop a model integrating inositol signaling in the known signal transduction pathways governed by Ras, G-protein coupled receptors, cAMP and elucidate different roles in development.

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Unified rhombic lip origins of Group 3 and Group 4 medulloblastoma

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Unified rhombic lip origins of Group 3 and Group 4 medulloblastoma [OTX2_KO]

Project description:RNA-seq profiling of medulloblastoma OTX-knockout.

2022-09-23 | GSE209919 | GEO

Group-specific cellular metabolism in Medulloblastoma

Project description:Background Cancer metabolism influences multiple aspects of tumorigenesis and causes diversity across malignancies. Although comprehensive research has extended our knowledge of molecular subgroups in medulloblastoma (MB), discrete analysis of metabolic heterogeneity is currently lacking. This study seeks to improve our understanding of metabolic phenotypes in MB and their impact on patients’ outcomes. Methods Data from four independent MB cohorts encompassing 1,288 patients were analysed. We explored metabolic characteristics of 902 patients (ICGC and MAGIC cohorts) on bulk RNA level. Moreover, data from 491 patients (ICGC cohort) were searched for DNA alterations in genes regulating cell metabolism. To determine the role of intratumoral metabolic differences, we examined single-cell RNA-sequencing (scRNA-seq) data from 34 additional patients. Findings on metabolic heterogeneity were correlated to clinical data. Results Established MB groups exhibit substantial differences in metabolic gene expression. By employing unsupervised analyses, we identified three clusters of group 3 and 4 samples with distinct metabolic features in ICGC and MAGIC cohorts. Analysis of scRNA-seq data confirmed our results of intertumoral heterogeneity underlying the according differences in metabolic gene expression. On DNA level, we discovered clear associations between altered regulatory genes involved in MB development and lipid metabolism. Additionally, we determined the prognostic value of metabolic gene expression in MB and showed that expression of genes involved in metabolism of inositol phosphates and nucleotides correlates with patient survival. Conclusion Our research underlines the biological and clinical relevance of metabolic alterations in MB. Thus, distinct metabolic signatures presented here might be the first step towards future metabolism-targeted therapeutic options.

2023-06-06 | GSE212559 | GEO

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