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MRNA array of CRISPR-Cas9 medicated ATRX gene editing in glioma cells

ABSTRACT: Glioma is the most common primary malignant brain tumor in adults. Chemo resistance of temozolomide (TMZ), the first-line chemotherapeutic agent, is a major issue in the management of patients with glioma. Alterations of ATRX constitute one of the most prevalent genetic abnormalities in gliomas. Therefore, it is urgent to further elucidate the role of ATRX contributing to TMZ resistance in glioma. We used microarrays to detail the global programme of gene expression underlying cellularisation and identified distinct classes of up-regulated and down-regulated genes after ATRX knockout.

ORGANISM(S): Homo sapiens

PROVIDER: GSE131781 | GEO | 2020/03/30

REPOSITORIES: GEO

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Class I HDAC overexpression promotes temozolomide resistance in glioma cells by regulating RAD18 expression

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2022-04-01 | PXD028683 | Pride

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2020-07-04 | GSE100775 | GEO

Microarray analysis of U87 glioma cells after transient knockdown of FOXM1

2012-08-11 | GSE40051 | GEO

LncRNA and mRNA expression data from TMZ-resistant cell line

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2020-07-03 | GSE100736 | GEO

Disruption of DNA Repair and Survival Pathways through Heat Shock Protein inhibition by Onalespib to Sensitize Malignant Gliomas to Chemoradiation therapy

Project description:Purpose: Proficient DNA repair by homologous recombination (HR) facilitates resistance to chemo-radiation in glioma stem cells (GSCs). We evaluated whether compromising HR by targeting HSP90, a molecular chaperone required for the function of key HR proteins, using onalespib, a long-acting, brain-penetrant HSP90 inhibitor, would sensitize high-grade gliomas to chemo-radiation in vitro and in vivoExperimental Design: The ability of onalespib to deplete HR client proteins, impair HR repair capacity, and sensitize GBM to chemo-radiation was evaluated in vitro in GSCs, and in vivo using zebrafish and mouse intracranial glioma xenograft models. The effects of HSP90 inhibition on the transcriptome and cytoplasmic proteins was assessed in GSCs and in ex vivo organotypic human glioma slice cultures.Results: Treatment with onalespib depleted CHK1 and RAD51, two key proteins of the HR pathway, and attenuated HR repair, sensitizing GSCs to the combination of radiation and temozolomide (TMZ). HSP90 inhibition reprogrammed the transcriptome of GSCs and broadly altered expression of cytoplasmic proteins including known and novel client proteins relevant to GSCs. The combination of onalespib with radiation and TMZ extended survival in a zebra fish and a mouse xenograft model of GBM compared to the standard of care (radiation and TMZ) or onalespib with radiation.Conclusions: The results of this study demonstrate that targeting HR by HSP90 inhibition sensitizes GSCs to radiation and chemotherapy and extends survival in zebrafish and mouse intracranial models of GBM. These results provide a preclinical rationale for assessment of HSP90 inhibitors in combination with chemoradiation in GBM patients.

2022-04-15 | GSE193635 | GEO

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