CHD7 promotes glioblastoma cell motility and invasiveness through transcriptional modulation of an invasion signature
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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.
Machado RA.C., Schneider H, De Ocesano-Pereira C, Lichtenstein F, Andrade F, Fujita A, et al. CHD7 promotes glioblastoma cell motility and invasiveness through transcriptional modulation of an invasion signature. Sci Rep. 2019 Mar;9:3952. doi:10.1038/s41598-019-39564-w.
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) ; Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) ; Financiadora de Estudos e Projetos (FINEP) ; Banco Nacional de Desenvolvimento Econômico e Social (BNDES) ; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
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