Dataset Information

GFAP?/GFAP? ratio directs astrocytoma gene expression towards a more malignant profile.

ABSTRACT: Astrocytomas are the most common malignant brain tumours and are to date incurable. It is unclear how astrocytomas progress into higher malignant grades. The intermediate filament cytoskeleton is emerging as an important regulator of malignancy in several tumours. The majority of the astrocytomas express the intermediate filament protein Glial Fibrillary Acidic Protein (GFAP). Several GFAP splice variants have been identified and the main variants expressed in human astrocytoma are the GFAP? and GFAP? isoforms. Here we show a significant downregulation of GFAP? in grade IV astrocytoma compared to grade II and III, resulting in an increased GFAP?/? ratio. Mimicking this increase in GFAP?/? ratio in astrocytoma cell lines and comparing the subsequent transcriptomic changes with the changes in the patient tumours, we have identified a set of GFAP?/? ratio-regulated high-malignant and low-malignant genes. These genes are involved in cell proliferation and protein phosphorylation, and their expression correlated with patient survival. We additionally show that changing the ratio of GFAP?/?, by targeting GFAP expression, affected expression of high-malignant genes. Our data imply that regulating GFAP expression and splicing are novel therapeutic targets that need to be considered as a treatment for astrocytoma.

SUBMITTER: Stassen OMJA

PROVIDER: S-EPMC5675697 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

GFAPδ/GFAPα ratio directs astrocytoma gene expression towards a more malignant profile.

Stassen Oscar M J A OMJA van Bodegraven Emma J EJ Giuliani Fabrizio F Moeton Martina M Kanski Regina R Sluijs Jacqueline A JA van Strien Miriam E ME Kamphuis Willem W Robe Pierre A J PAJ Hol Elly M EM

Oncotarget 20171004 50

Astrocytomas are the most common malignant brain tumours and are to date incurable. It is unclear how astrocytomas progress into higher malignant grades. The intermediate filament cytoskeleton is emerging as an important regulator of malignancy in several tumours. The majority of the astrocytomas express the intermediate filament protein Glial Fibrillary Acidic Protein (GFAP). Several <i>GFAP</i> splice variants have been identified and the main variants expressed in human astrocytoma are the <i ...[more]

PMID: 29152145

Similar Datasets

Project description:Malignant astrocytoma (MA) is the most common and severe type of brain tumor. A greater understanding of the underlying mechanisms responsible for the development of MA would be beneficial for the development of targeted molecular therapies. In the present study, the upregulated differentially expressed genes (DEGs) in MA were obtained from the Gene Expression Omnibus database using R/Bioconductor software. DEGs in different World Health Organization classifications were compared using the Venny tool and 15 genes, including collagen type I ?1 chain (COL1A1) and laminin subunit ?1 (LAMC1), were revealed to be involved in the malignant progression of MA. In addition, the upregulated DEGs in MA were evaluated using functional annotations of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes with the Database for Annotation, Visualization, and Integrated Discovery tool. The results indicated that invasion?associated enrichment was observed in 'extracellular matrix' (ECM), 'cell adhesion' and 'phosphoinositide 3?kinase?protein kinase B signaling pathway'. Subsequently, the analysis of the protein?protein interactions was performed using STRING and Cytoscape software, which revealed that the ECM component was the invasion?associated module and its corresponding genes included COL1A1, LAMC1 and fibronectin 1. Finally, survival Kaplan?Meier estimate was conducted using cBioportal online, which demonstrated that COL1A1 expression affected the survival of and recurrence in patients with MA. Moreover, the results of in vitro Transwell assay and western blot analysis revealed that the depleted levels of COL1A1 also decreased the expression of several proteins associated with cell invasion, including phosphorylated?signal transducer and activator of transcription 3, matrix metalloproteinase (MMP)?2, MMP?9 and nuclear factor??B. On the whole, the present study identified the invasion?related target genes and the associated potential pathways in MA. The results indicated that COL1A1 may be a candidate biomarker for the prognosis and treatment of MA.

Dataset Information

GFAP?/GFAP? ratio directs astrocytoma gene expression towards a more malignant profile.

Publications

GFAPδ/GFAPα ratio directs astrocytoma gene expression towards a more malignant profile.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets