CHD7 promotes glioblastoma cell motility and invasiveness through transcriptional modulation of an invasion signature
Sci Rep, v. 9, 3952, mar. 2019
Article
en En
| SES-SP, SESSP-IBPROD, SES-SP
| ID: bud-2685
Biblioteca responsable:
BR78.1
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.
Texto completo:
1
Colección:
06-national
/
BR
Base de datos:
SES-SP
/
SESSP-IBPROD
Idioma:
En
Revista:
Sci Rep
Año:
2019
Tipo del documento:
Article