Artículo
en Inglés
| SES-SP, SESSP-IBPROD, SES-SP | ID: but-ib15862
Chromatin remodeler proteins exert an important function in promoting dynamic modifications in the chromatinarchitecture, 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 humancancers. However, its potential role in glioblastoma has not yet been tested. Here, we show that CHD7 is up-regulated in humangliomatissues and we demonstrate that CHD7 knockout (KO) in LN-229 glioblastomacells suppresses anchorage-independent growth and spheroid invasion in vitro. Additionally, CHD7 KO impairs tumorgrowth and increases overall survival in an orthotopic mousexenograft model. Conversely, ectopic overexpression of CHD7 in LN-428 and A172 glioblastomacell lines increases cell motility and invasiveness in vitro and promotes LN-428 tumorgrowth in vivo. Finally, RNA-seqanalysis revealed that CHD7 modulates a specific transcriptional signature of invasion-related target genes. Further studies should explore clinical-translational implications for glioblastomatreatment.