Epigenetic-focused CRISPR-Cas9 screen identifies ASH2L as a regulator of Glioblastoma cell survival
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ABSTRACT: Glioblastoma Multiforme (GBM) is the most common and aggressive primary brain tumor. Despite recent developments in surgery, chemo- and radiotherapy, a currently poor prognosis of GBM patients highlights an urgent need for novel treatment strategies. Our awareness on importance of epigenetic mechanisms for tumor initiation, progression and apoptotic response lead us to investigate epigenetic regulators of GBM survival through a genetic ablation screen. Screen with our custom library EPIDOKOL targeting functional domains of critical chromatin modifier genes, revealed multiple GBM essentiality gene candidates, most importantly ASH2L. Upon ASH2L ablation, we observed induction of apoptosis and cell cycle arrest concomitant with a set of downregulated signature genes. Massive reduction in tumor forming capacity of ASH2L depleted GBM cells as well as high ASH2L expression in GBM patients in comparison to low grade gliomas (LGG) proved essentiality of the gene for glioma cell fitness. Detection of epigenetic factors modulating tumor survival via high throughput, robust and affordable screens such as EPIDOKOL holds great promise to ultimately enable rapid discovery of novel cancer biomarkers and production of effective therapies which will increase life span and dignity of cancer patients.
INSTRUMENT(S): Orbitrap Fusion Lumos
ORGANISM(S): Homo Sapiens (human)
TISSUE(S): Brain
SUBMITTER: Tugba Bagci Onder
LAB HEAD: Tugba Bagci Onder
PROVIDER: PXD033358 | Pride | 2024-01-26
REPOSITORIES: Pride
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