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Group-specific cellular metabolism in Medulloblastoma

ABSTRACT: Group-specific cellular metabolism in Medulloblastoma

PROVIDER: PRJNA875953 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR21391300.fastq.gz	Fastqsanger.gz
	SRR21391301.fastq.gz	Fastqsanger.gz
	SRR21391302.fastq.gz	Fastqsanger.gz
	SRR21391303.fastq.gz	Fastqsanger.gz
	SRR21391304.fastq.gz	Fastqsanger.gz

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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

Group-specific cellular metabolism in Medulloblastoma.

Project description:BackgroundCancer 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.MethodsData 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.ResultsEstablished 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.ConclusionOur 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.

| S-EPMC10242934 | biostudies-literature

Downregulation of CRX, a Group 3 specific oncogenic transcription factor, inhibits TGF-b/activin signaling in medulloblastoma cells

Project description:Retina-specific gene expression is the distinguishing characteristic of Group 3 medulloblastoma. CRX, a homeobox transcription factor, is overexpressed specifically in Group 3 tumors. ShRNA-mediated CRX knockdown decreased the expression of seveal retina-specific genes and Group 3 specific genes. CRX knockdown inhibited the TGF-beta/activin signaling pathway, which is known to play oncogenic role in a subset of Group 3 medulloblastoma

2021-08-26 | GSE174620 | GEO

Prtg+ve Rhombic Lip Ventricular Zone Stem Cells Initiate and Maintain Group 3 Medulloblastoma

Project description:PRTG+ve cells show high self renewability in Group 3 medulloblastoma tumors. To access the proteins differentially expressed in this subset of cells, we sorted PRTG+ve and PRTG-ve cells by surface staining with Anti-PRTG antibody from Gr3 medulloblastoma xenografts.

2024-07-31 | PXD034890 | Pride

miRNA expression profiles of pediatric medulloblastoma

Project description:The main cause of death in medulloblastoma is recurrence associated with leptomeningeal dissemination. Although the molecular basis of medulloblastoma has received considerable attention over the past decade, the role of microRNAs (miRNAs) in the acquisition of metastatic phenotype remains poorly understood. This study aimed to identify miRNA involved in leptomeningeal dissemination and to elucidate its target mechanisms. We analyzed miRNA expression profiles of 29 medulloblastomas according to the presence of cerebrospinal fluid (CSF) seeding. The differential expressed miRNAs (DEmiRNAs) were validated on 29 medulloblastoma tissues and three medulloblastoma cells. The biological function of the selected miRNA was evaluated using in vitro studies. A total of 12 DEmiRNAs were identified including miRNA-192 in medulloblastoma with seeding. The reduced expression of miRNA-192 was confirmed in tumor seeding group and the medulloblastoma cells. Overexpression of miRNA-192 inhibited cellular proliferation targeting dihydrofolate reductase (DHFR). MiRNA-192 decreased cellular anchoring via repression of integrin subunits (Î±V, Î²1, and Î²3) and CD47. Medulloblastoma with seeding showed specific DEmiRNAs compared with those without seeding. MicroRNA-192 suppresses leptomeningeal dissemination of medulloblastoma through modulating cell proliferation and anchoring ability. leptomeningeal dissemination in 29 pediatric medulloblastoma patients

2015-12-31 | E-GEOD-66968 | biostudies-arrayexpress

Effect of ZIC1 on group 3 medulloblastoma cell lines and granule neuron progenitor [ChIP-seq]

Project description:Investigate the DNA binding pattern as well as transcriptional consequences of ZIC1 and its medulloblastoma mutants in group 3 medulloblastoma cell lines and granule neuron progenitors

2024-09-19 | GSE217638 | GEO

Effect of ZIC1 on group 3 medulloblastoma cell lines and granule neuron progenitor [RNA-seq]

2024-09-19 | GSE217571 | GEO

Remodeling Group 3 medulloblastoma: MYC overexpression alone transforms progenitors of astrocytes and granule neurons in the postnatal cerebellum

Project description:Group 3 medulloblastoma is often associated with MYC amplification or overexpression, while whether MYC overexpression alone is sufficient to induce tumorigenesis is unknown and the cell type(s) which can be transformed by MYC is unclear. Here, by generating a new mouse model, we demonstrated that overexpression of Myc alone is sufficient to transform astrocyte progenitors and granule neuron progenitors (GNP) in the early postnatal cerebellum following orthotopic transplantation. The resulting tumors resemble human Group 3 medulloblastoma in terms of both histology and gene expression profiles. Using these models we found that inhibition of lactate dehydrogenase A (LDHA) significantly reduced both murine and human MYC-driven tumor growth, but did not affect SHH medulloblastoma, indicating that LDHA is potential and specific therapeutic target for MYC-driven medulloblastoma.

2019-04-25 | GSE114760 | GEO

Transcriptome analysis of Group 3 and 4 medulloblastoma orthotopic xenograft mice with digoxin treatment

Project description:RNA-seq data of Group 3 and 4 medulloblastoma with digoxin treatment.

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An OTX2-PAX3 signaling axis regulates Group 3 medulloblastoma cell fate [ChIP-seq]

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2020-06-11 | GSE132269 | GEO

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