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Protein arginine methyltransferase 5 (PRMT5) is an actionable therapeutic target in CDK4/6 inhibitor-resistant ER+/RB-deficient breast cancer [RNA-seq_Pemrametostat]

ABSTRACT: Protein arginine methyltransferase 5 (PRMT5) is an actionable therapeutic target in CDK4/6 inhibitor-resistant ER+/RB-deficient breast cancer [RNA-seq_Pemrametostat]

PROVIDER: PRJNA991484 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR25146204_1.fastq.gz	Fastqsanger.gz
	SRR25146204_2.fastq.gz	Fastqsanger.gz
	SRR25146205_1.fastq.gz	Fastqsanger.gz
	SRR25146205_2.fastq.gz	Fastqsanger.gz
	SRR25146206_1.fastq.gz	Fastqsanger.gz

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Protein arginine methyltransferase 5 (PRMT5) is an actionable therapeutic target in CDK4/6 inhibitor-resistant ER+/RB-deficient breast cancer [RNA-seq_siPRMT5]

Project description:CDK4/6 inhibitors (CDK4/6i) have improved survival of patients with estrogen receptor-positive (ER+) breast cancer. However, patients treated with CDK4/6i eventually develop drug resistance and progress. RB1 loss-of-function alterations confer resistance to CDK4/6i, but the optimal therapy for these patients is unclear. Through a genome-wide CRISPR screen, we identified protein arginine methyltransferase 5 (PRMT5) as a molecular vulnerability in ER+/RB1-knockout (RBKO) breast cancer cells. Inhibition of PRMT5 blocked the G1-to-S transition in the cell cycle independent of RB, leading to growth arrest in RBKO cells. Proteomics analysis uncovered fused in sarcoma (FUS) as a downstream effector of PRMT5. Inhibition of PRMT5 resulted in dissociation of FUS from RNA polymerase II (Pol II), which led to Ser2 Pol II hyperphosphorylation, intron retention, and subsequent downregulation of proteins involved in DNA synthesis. Furthermore, treatment with the PRMT5 inhibitor pemrametostat and a selective ER degrader fulvestrant synergistically inhibited growth of ER+/RB-deficient cell-derived and patient-derived xenografts. These findings highlight the potential of dual ER and PRMT5 blockade as a novel therapeutic strategy to overcome resistance to CDK4/6i in ER+/RB-deficient breast cancer.

2023-07-11 | GSE236499 | GEO

Protein arginine methyltransferase 5 (PRMT5) is an actionable therapeutic target in CDK4/6 inhibitor-resistant ER+/RB-deficient breast cancer [RNA-seq_Pemrametostat]

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Protein arginine methyltransferase 5 (PRMT5) is an actionable therapeutic target in CDK4/6 inhibitor-resistant ER+/RB-deficient breast cancer [RNA-seq_RBKO vs WT]

2023-07-11 | GSE236498 | GEO

Protein arginine methyltransferase 5 (PRMT5) is an actionable therapeutic target in CDK4/6 inhibitor-resistant ER+/RB-deficient breast cancer [pSer2 Pol II ChIP-seq]

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Protein arginine methyltransferase 5 (PRMT5) is an actionable therapeutic target in CDK4/6 inhibitor-resistant ER+/RB-deficient breast cancer

Project description:Protein arginine methyltransferase 5 (PRMT5) is an actionable therapeutic target in CDK4/6 inhibitor-resistant ER+/RB-deficient breast cancer

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Protein arginine methyltransferase 5 (PRMT5) is an actionable therapeutic target in CDK4/6 inhibitor-resistant ER+/RB-deficient breast cancer [RNA-seq_siPRMT5]

Project description:Protein arginine methyltransferase 5 (PRMT5) is an actionable therapeutic target in CDK4/6 inhibitor-resistant ER+/RB-deficient breast cancer [RNA-seq_siPRMT5]

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Protein arginine methyltransferase 5 (PRMT5) is an actionable therapeutic target in CDK4/6 inhibitor-resistant ER+/RB-deficient breast cancer [RNA-seq_RBKO vs WT]

Project description:Protein arginine methyltransferase 5 (PRMT5) is an actionable therapeutic target in CDK4/6 inhibitor-resistant ER+/RB-deficient breast cancer [RNA-seq_RBKO vs WT]

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Protein arginine methyltransferase 5 (PRMT5) is an actionable therapeutic target in CDK4/6 inhibitor-resistant ER+/RB-deficient breast cancer [pSer2 Pol II ChIP-seq]

Project description:Protein arginine methyltransferase 5 (PRMT5) is an actionable therapeutic target in CDK4/6 inhibitor-resistant ER+/RB-deficient breast cancer [pSer2 Pol II ChIP-seq]

| PRJNA991485 | ENA

Protein arginine methyltransferase 5 (PRMT5) is an actionable therapeutic target in CDK4/6 inhibitor-resistant ER+/RB-deficient breast cancer

Project description:PRMT5 Co-IP mass spectrometry: Lysates of MCF-7 RB1-knockout cells were pulled down with a PRMT5 antibody or IgG control. The pulldowns were subjected to mass spectrometry analysis. QEX2_981005, QEX2_981006, QEX2_981007: DMSO, IgG QEX2_981008, QEX2_981009, QEX2_981010: DMSO, PRMT5 antibody QEX2_981011, QEX2_981012, QEX2_981013, GSK, IgG QEX2_981014, QEX2_981015, QEX2_981016, GSK, PRMT5 antibody SDMA PTM analysis: MCF-7 RB1-knockout cells were transfected with a PRMT5 siRNA or a control siRNA. Lysates were collected three days after transfection and subjected to mass spectrometry analysis. LUM1_1000791, LUM1_1000792, LUM1_1000793: control SiRNA LUM1_1000794, LUM1_1000795, LUM1_1000796: PRMT5 siRNA [

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Protein arginine methyltransferase 5 (PRMT5) is an actionable therapeutic target in CDK4/6 inhibitor-resistant ER+/RB-deficient breast cancer

2023-06-30 | MSV000092321 | MassIVE