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  • BPTF regulates growth of adult and pediatric high-grade glioma through the MYC pathway.

BPTF regulates growth of adult and pediatric high-grade glioma through the MYC pathway.

Oncogene (2019-12-18)
Adam L Green, John DeSisto, Patrick Flannery, Rakeb Lemma, Aaron Knox, Madeleine Lemieux, Bridget Sanford, Rebecca O'Rourke, Shakti Ramkissoon, Kristen Jones, Jennifer Perry, Xu Hui, Erin Moroze, Ilango Balakrishnan, Allison F O'Neill, Katherine Dunn, Deborah DeRyckere, Etienne Danis, Aaron Safadi, Ahmed Gilani, Benjamin Hubbell-Engler, Zachary Nuss, Jean M Mulcahy Levy, Natalie Serkova, Sujatha Venkataraman, Douglas K Graham, Nicholas Foreman, Keith Ligon, Ken Jones, Andrew L Kung, Rajeev Vibhakar
ABSTRACT

High-grade gliomas (HGG) afflict both children and adults and respond poorly to current therapies. Epigenetic regulators have a role in gliomagenesis, but a broad, functional investigation of the impact and role of specific epigenetic targets has not been undertaken. Using a two-step, in vitro/in vivo epigenomic shRNA inhibition screen, we determine the chromatin remodeler BPTF to be a key regulator of adult HGG growth. We then demonstrate that BPTF knockdown decreases HGG growth in multiple pediatric HGG models as well. BPTF appears to regulate tumor growth through cell self-renewal maintenance, and BPTF knockdown leads these glial tumors toward more neuronal characteristics. BPTF's impact on growth is mediated through positive effects on expression of MYC and MYC pathway targets. HDAC inhibitors synergize with BPTF knockdown against HGG growth. BPTF inhibition is a promising strategy to combat HGG through epigenetic regulation of the MYC oncogenic pathway.

MATERIALS
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Product Description

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MISSION® pLKO.1-puro Luciferase shRNA Control Plasmid DNA, shRNA sequence targeting luciferase
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L-(−)-Glucose, ≥99%
Sigma-Aldrich
MISSION® TRC2 pLKO.5-puro Non-Target shRNA Control Plasmid DNA, Targets no known genes from any species