CHD7 promotes glioblastoma cell motility and invasiveness through transcriptional modulation of an invasion signature View Full Text


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Article Info

DATE

2019-12

AUTHORS

Raquel A. C. Machado, Hannah Schneider, Carlos DeOcesano-Pereira, Flavio Lichtenstein, Fernando Andrade, André Fujita, Marina Trombetta-Lima, Michael Weller, Christian Bowman-Colin, Mari Cleide Sogayar

ABSTRACT

Chromatin remodeler proteins exert an important function in promoting dynamic modifications in the chromatin architecture, performing a central role in regulating gene transcription. Deregulation of these molecular machines may lead to striking perturbations in normal cell function. The CHD7 gene is a member of the chromodomain helicase DNA-binding family and, when mutated, has been shown to be the cause of the CHARGE syndrome, a severe developmental human disorder. Moreover, CHD7 has been described to be essential for neural stem cells and it is also highly expressed or mutated in a number of human cancers. However, its potential role in glioblastoma has not yet been tested. Here, we show that CHD7 is up-regulated in human glioma tissues and we demonstrate that CHD7 knockout (KO) in LN-229 glioblastoma cells suppresses anchorage-independent growth and spheroid invasion in vitro. Additionally, CHD7 KO impairs tumor growth and increases overall survival in an orthotopic mouse xenograft model. Conversely, ectopic overexpression of CHD7 in LN-428 and A172 glioblastoma cell lines increases cell motility and invasiveness in vitro and promotes LN-428 tumor growth in vivo. Finally, RNA-seq analysis revealed that CHD7 modulates a specific transcriptional signature of invasion-related target genes. Further studies should explore clinical-translational implications for glioblastoma treatment. More... »

PAGES

3952

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41598-019-39564-w

    DOI

    http://dx.doi.org/10.1038/s41598-019-39564-w

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1112641485

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30850678


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    RDF/XML is a standard XML format for linked data.

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