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A genome-wide CRISPR activation screen identifies PRRX2 as a regulator of enzalutamide resistance in prostate cancer [RNA-seq]

ABSTRACT: A genome-wide CRISPR activation screen identifies PRRX2 as a regulator of enzalutamide resistance in prostate cancer [RNA-seq]

PROVIDER: PRJNA820699 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR18502800_1.fastq.gz	Fastqsanger.gz
	SRR18502800_2.fastq.gz	Fastqsanger.gz
	SRR18502789_1.fastq.gz	Fastqsanger.gz
	SRR18502789_2.fastq.gz	Fastqsanger.gz
	SRR18502790_1.fastq.gz	Fastqsanger.gz

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A genome-wide CRISPR activation screen identifies PRRX2 as a regulator of enzalutamide resistance in prostate cancer [RNA-seq]

Project description:We report that PRRX2 mediates enzalutamide resistance by activating the anti-apoptotic BCL2 and theE2F/RB1 cell cycle pathways.

2022-03-30 | GSE199538 | GEO

A genome-wide CRISPR activation screen identifies PRRX2 as a regulator of enzalutamide resistance in prostate cancer [ATAC-seq]

Project description:We report that PRRX2 mediates enzalutamide resistance by activating the anti-apoptotic BCL2 and theE2F/RB1 cell cycle pathways.

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A genome-wide CRISPR activation screen identifies PRRX2 as a regulator of enzalutamide resistance in prostate cancer

Project description:A genome-wide CRISPR activation screen identifies PRRX2 as a regulator of enzalutamide resistance in prostate cancer

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A genome-wide CRISPR activation screen identifies PRRX2 as a regulator of enzalutamide resistance in prostate cancer [ATAC-seq]

Project description:A genome-wide CRISPR activation screen identifies PRRX2 as a regulator of enzalutamide resistance in prostate cancer [ATAC-seq]

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A Genome-Wide CRISPR Activation Screen Identifies PRRX2 as a Regulator of Enzalutamide Resistance in Prostate Cancer.

Project description:Androgen receptor (AR) pathway inhibitors are the mainstay treatment for advanced prostate cancer, but resistance to therapy is common. Here, we used a CRISPR activation screen in metastatic castration-sensitive prostate cancer cells to identify genes that promote resistance to AR inhibitors. Activation of the TGFβ target gene paired-related homeobox2 (PRRX2) promoted enzalutamide resistance. PRRX2 expression was the highest in double-negative prostate cancer (DNPC), which lack AR signaling and neuroendocrine differentiation, and a PRRX2-related gene signature identified a subset of patients with DNPC with reduced overall survival. PRRX2-expressing cells showed alterations in the CDK4/6/Rb/E2F and BCL2 pathways. Accordingly, treatment with CDK4/6 and BCL2 inhibitors sensitized PRRX2-expressing, castration-resistant tumors to enzalutamide. Overall, PRRX2 was identified as a driver of enzalutamide resistance. The PRRX2 signature merits investigation as a biomarker of enzalutamide resistance in prostate cancer that could be reversed with CDK4/6 and BCL2 inhibitors.SignificancePRRX2 mediates enzalutamide resistance via activation of the E2F and BCL2 pathways, which can be targeted with CDK4/6 and BCL2 inhibitors to reverse resistance.

| S-EPMC9177667 | biostudies-literature

Genome-wide CRISPR Knockout Screen in LNCaP Cells Treated with Enzalutamide

Project description:To categorize gene loss events in enzalutamide-treated LNCaP cells, a genome-wide CRISPR knockout (KO) screen was performed. We quantified sgRNA abundance between initial and final timepoints in DMSO and enzalutamide treated cell populations

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A genome-wide CRISPR activation screen identifies PRRX2 as a regulator of enzalutamide resistance in prostate cancer

Project description:This SuperSeries is composed of the SubSeries listed below.

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A kinome-wide CRISPR screen identifies CK1α as a novel target to overcome enzalutamide resistance of prostate cancer

Project description:Utilizing a kinome-wide CRISPR-Cas9 knockout screen, we identified casein kinase 1 alpha (CK1α) as a novel therapeutic target to overcome enzalutamide resistance. To dissect the underlying mechanisms of targeting CK1α to sensitize cancer cells to ENZA, we performed RNA sequencing of 22Rv1 cells upon CK1α knockout or overexpression. We found that CK1α regulated double-strand break (DSB)-response signaling.

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Identification of Selective SWI/SNF Dependencies in Enzalutamide-Resistant Prostate Cancer [CRISPR Screen]

Project description:Identification of Selective SWI/SNF Dependencies in Enzalutamide-Resistant Prostate Cancer [CRISPR Screen]

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Genome-wide CRISPR Knockout Screen in LNCaP Cells Treated with Enzalutamide

Project description:Genome-wide CRISPR Knockout Screen in LNCaP Cells Treated with Enzalutamide

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