Bone morphogenetic protein-7 is a MYC target with prosurvival functions in childhood medulloblastoma.

摘要: Medulloblastoma (MB) is the most common malignant brain tumor in children. It known that overexpression and/or amplification of MYC oncogene associated with poor clinical outcome, but molecular mechanisms and downstream effectors MB remain still elusive. Besides contributing to elucidate how progression takes place, importantly, identification novel MYC-target genes will suggest candidates for targeted therapy MB. A group 209 MYC-responsive was obtained from a complementary DNA microarray analysis MB-derived cell line, following silencing. Among genes, we identified members bone morphogenetic protein (BMP) signaling pathway, which have crucial role during development cerebellum. In particular, gene BMP7 as direct target MYC. positive correlation between expression documented by analyzing two distinct sets primary samples. Functional studies vitro using small-molecule inhibitor BMP/SMAD pathway reproduced effect small interfering RNA-mediated silencing BMP7. Both approaches led block proliferation panel cells inhibition SMAD phosphorylation. Altogether, our findings indicate high levels drive overexpression, promoting survival cells. This observation suggests potential relevance targeting therapeutic approach treatment childhood