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

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.

journal_name

Oncogene

journal_title

Oncogene

authors

Green AL,DeSisto J,Flannery P,Lemma R,Knox A,Lemieux M,Sanford B,O'Rourke R,Ramkissoon S,Jones K,Perry J,Hui X,Moroze E,Balakrishnan I,O'Neill AF,Dunn K,DeRyckere D,Danis E,Safadi A,Gilani A,Hubbell-Engler B,Nus

doi

10.1038/s41388-019-1125-7

subject

Has Abstract

pub_date

2020-03-01 00:00:00

pages

2305-2327

issue

11

eissn

0950-9232

issn

1476-5594

pii

10.1038/s41388-019-1125-7

journal_volume

39

pub_type

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