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Polycomb-mediated repression of EphrinA5 promotes growth and invasion of glioblastoma

ABSTRACT: Glioblastoma (GBM) is the most common and most aggressive intrinsic brain tumour in adults. Integrated transcriptomic and epigenomic analyses of glioblastoma initiating cells (GIC) in a mouse model uncovered a novel epigenetic regulation of EfnA5. In this model, Bmi1 enhances H3K27me3 at the EfnA5 locus and reinforces repression of selected target genes in a cellular context dependent fashion. EfnA5 mediate Bmi1-dependent proliferation and invasion in vitro and tumour formation in an allograft model. Importantly, we show that this novel Polycomb feed-forward loop is also active in human GIC and we provide preclinical evidence of druggability of EFNA5 in GBM xenografts overexpressing BMI1.

ORGANISM(S): Mus musculus

PROVIDER: GSE141961 | GEO | 2020/02/01

REPOSITORIES: GEO

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