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Genome-wide CRISPR/Cas9 loss-of-function screen for prostate cancer cell line

ABSTRACT: Prostate cancer (PCa) is the most frequently diagnosed malignancy in men worldwide. Epigenetic regulation has been recognized as a main mechanism of cancer evolution. PRMT5 is the major type II protein arginine methyltransferase catalyzing the symmetric dimethylation of arginine in mammalian. PRMT5 is found upregulated in PCa. However, its exact functional contribution to prostate tumorigenesis is unknown. PRMT5 inhibition via pharmacological inhibition (EPZ015666) reduces stemness with paralleled differentiation and arrests cell cycle progression but without causing appreciable apoptosis.To understand the mechanisms of cell tolerance to PRMT5 inhibition and to identify potential pathways that function synergistically with EPZ015666, we performed a genome-wide CRISPR/Cas9 loss-of-function screen in the presence of EPZ015666. Our data unravel that many clinical-grade drugs of known oncogenic pathways can be repurposed to target castration-resistant PCa when used in synergy with EPZ015666 at low doses. Genome-wide CRISPR/Cas9 loss-of-function screen in the presence of EPZ015666 in DU145

ORGANISM(S): Homo sapiens

PROVIDER: GSE222018 | GEO | 2024/09/03

REPOSITORIES: GEO

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