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
Oncogenejournal_title
Oncogeneauthors
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,Nusdoi
10.1038/s41388-019-1125-7subject
Has Abstractpub_date
2020-03-01 00:00:00pages
2305-2327issue
11eissn
0950-9232issn
1476-5594pii
10.1038/s41388-019-1125-7journal_volume
39pub_type
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