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E-GEOD-74622 - BRG1/SMARCA4 is essential for neuroblastoma cell viability through modulation of cell death and survival pathways

Status
Released on 1 March 2016, last updated on 5 March 2016
Organism
Homo sapiens
Samples (6)
Array (1)
Protocols (7)
Description
Neuroblastoma (NB) is a neoplasm of the sympathetic nervous system, and is the most common solid tumor of infancy. NBs are very heterogeneous, with a clinical course ranging from spontaneous regression to resistance to all current forms of treatment. High-risk patients need intense chemotherapy, and only 30-40% will be cured. Relapsed or metastatic tumors acquire multi-drug resistance, raising the need for alternative treatments. Owing to the diverse mechanisms that are responsible of NB chemoresistance, we aimed to target epigenetic factors that control multiple pathways to bypass therapy resistance. We found that the SWI/SNF-related, matrix-associated, actin- dependent regulator of chromatin, subfamily a, member 4 (SMARCA4/BRG1) was consistently upregulated in advanced stages of NB, with high BRG1 levels being indicative of poor outcome. Loss-of-function experiments in vitro and in vivo showed that BRG1 is essential for the proliferation of NB cells. Furthermore, whole genome transcriptome analysis revealed that BRG1 controls the expression of key elements of oncogenic pathways such as PI3K/AKT and BCL2, which offers a promising new combination therapy for high-risk NB Non-silencing control (NSC) or shBRG1 lentiviral vectors were transduced in the Neuroblastoma cell lines SK-N-BE(2) by triplicate. 48h post-infection, total RNA was extracted
Experiment type
transcription profiling by array 
Contacts
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-74622.idf.txt
Sample and data relationshipE-GEOD-74622.sdrf.txt
Raw data (1)E-GEOD-74622.raw.1.zip
Processed data (1)E-GEOD-74622.processed.1.zip
Array designA-GEOD-16686.adf.txt
Links