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Bromodomain-containing protein BRPF1 as a therapeutic target for metastatic ovarian cancer

ABSTRACT: Bromodomain-containing protein BRPF1 as a therapeutic target for metastatic ovarian cancer

PROVIDER: PRJEB71498 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	ERR12387331_1.fastq.gz	Fastqsanger.gz
	ERR12387331_2.fastq.gz	Fastqsanger.gz
	ERR12387332_1.fastq.gz	Fastqsanger.gz
	ERR12387332_2.fastq.gz	Fastqsanger.gz
	ERR12387333_1.fastq.gz	Fastqsanger.gz

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Bromodomain-containing protein BRPF1 as a therapeutic target for metastatic ovarian cancer

Project description:Total RNA was extracted using TRIzol from PEO4 and OVCAR-3 cells treated for 72 hours with 10uM GSK6853 or DMSO as a control. In case of BRPF1 silencing experiment, RNA extraction was performed from cells transfected with BRPF-targeting siRNA or nontarget (scramble) siRNA 96 hours post-transfection using TRIzol and Zymo RNA Clean & Concentrator-5 columns. Indexed libraries were prepared starting from 1000 ng of total RNA according to Illumina Stranded Total RNA prep Ligation with Ribo-Zero Plus kit. Final libraries were sequenced at a concentration of 0,6 pM/lane on the Illumina Novaseq 6000 using S4 flowcell and v1.5 reagents. The current study was focused on the investigation of molecular mechanisms underlying the antiproliferative effect of BRPF1 inhibition or silencing in ovarian cancer. To this end, transcriptome changes induced by GSK6853 treatment in chemotherapy-resistant PEO4 and OVCAR-3 cells and BRPF1 silencing in OVCAR-3 cells were analysed.

2024-01-08 | E-MTAB-13663 | biostudies-arrayexpress

Essential gene screening identifies the Bromodomain-Containing Protein BRPF1 as a new therapeutic target for endocrine therapy-resistant breast cancer

Project description:Exploring epigenetic gene essentiality identifying key regulators of cell survival represents a promising way to exploit new targets to overcome resistance to current pharmacological regimens. In breast cancer (BC), endocrine therapy (ET) resistance arises from aberrant Estrogen Receptor alpha (ERα) signaling and targeting cancer cell vulnerability within the ERα pathway represents a rationale for development of effective new drugs against this disease. By combining bioinformatics analysis of genome-wide ‘drop-out’ screenings and siRNA-mediated gene knock-down (kd) we identified a set of essential genes that includes, as the most effective, the bromodomain containing protein BRPF1. BRPF1 belongs to a family of epigenetic readers acting as chromatin remodelers to control gene transcription. To gather mechanistic insight into the role of this epienzyme in BC, we applied chromatin and transcriptome profiling, gene ablation and specific pharmacological inhibition followed by cellular and functional assays. Experimental evidences indicate that BRPF1 associates with ERa in MCF-7 cells chromatin and its blockade inhibits cell cycle progression, reduces cell proliferation and mediates transcriptome changes through modulation of chromatin accessibility. This results in a widespread inhibition of ER-dependent hormonal signaling obtained by ERa gene silencing in AE-sensitive and -resistant BC cells and pre-clinical patient-derived models (PDO). The characterization of functional interplays between ERα and BRPF1 revealed a new master regulator of BC survival, providing a rationale for a BRPF1 targeted cancer diagnosis and highlighting a new therapeutic vulnerability for the treatment of these aggressive tumors.

2024-10-03 | E-MTAB-13884 | biostudies-arrayexpress

Essential gene screening identifies the Bromodomain-Containing Protein BRPF1 as a new therapeutic target for endocrine therapy-resistant breast cancer

2024-10-03 | E-MTAB-13885 | biostudies-arrayexpress

Essential gene screening identifies the Bromodomain-Containing Protein BRPF1 as a new therapeutic target for endocrine therapy-resistant breast cancer

2024-10-03 | E-MTAB-13876 | biostudies-arrayexpress

Essential gene screening identifies the Bromodomain-Containing Protein BRPF1 as a new therapeutic target for endocrine therapy-resistant breast cancer - organoids

2024-10-04 | E-MTAB-13887 | biostudies-arrayexpress

Bromodomain-containing protein BRPF1 is a therapeutic target for liver cancer.

Project description:Epigenetic deregulation plays an essential role in hepatocellular carcinoma (HCC) progression. Bromodomains are epigenetic "readers" of histone acetylation. Recently, bromodomain inhibitors have exhibited promising therapeutic potential for cancer treatment. Using transcriptome sequencing, we identified BRPF1 (bromodomain and PHD finger containing 1) as the most significantly upregulated gene among the 43 bromodomain-containing genes in human HCC. BRPF1 upregulation was significantly associated with poor patient survival. Gene ablation or pharmacological inactivation of BRPF1 significantly attenuated HCC cell growth in vitro and in vivo. BRPF1 was involved in cell cycle progression, senescence and cancer stemness. Transcriptome sequencing revealed that BRPF1 is a master regulator controlling the expression of multiple key oncogenes, including E2F2 and EZH2. We demonstrated that BRPF1 activated E2F2 and EZH2 expression by facilitating promoter H3K14 acetylation through MOZ/MORF complex. In conclusion, BRPF1 is frequently upregulated in human HCCs. Targeting BRPF1 may be an approach for HCC treatment.

| S-EPMC8292510 | biostudies-literature

Essential gene screening identifies the Bromodomain-Containing Protein BRPF1 as a new therapeutic target for endocrine therapy-resistant breast cancer

Project description:Essential gene screening identifies the Bromodomain-Containing Protein BRPF1 as a new therapeutic target for endocrine therapy-resistant breast cancer

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Essential gene screening identifies the Bromodomain-Containing Protein BRPF1 as a new therapeutic target for endocrine therapy-resistant breast cancer

Project description:Essential gene screening identifies the Bromodomain-Containing Protein BRPF1 as a new therapeutic target for endocrine therapy-resistant breast cancer

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Essential gene screening identifies the Bromodomain-Containing Protein BRPF1 as a new therapeutic target for endocrine therapy-resistant breast cancer

Project description:Essential gene screening identifies the Bromodomain-Containing Protein BRPF1 as a new therapeutic target for endocrine therapy-resistant breast cancer

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Essential gene screening identifies the Bromodomain-Containing Protein BRPF1 as a new therapeutic target for endocrine therapy-resistant breast cancer - organoids

Project description:Essential gene screening identifies the Bromodomain-Containing Protein BRPF1 as a new therapeutic target for endocrine therapy-resistant breast cancer - organoids

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