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Neuropilin-2 regulates androgen-receptor transcriptional activity in advanced prostate cancer [RNA-seq]

ABSTRACT: Neuropilin-2 regulates androgen-receptor transcriptional activity in advanced prostate cancer [RNA-seq]

PROVIDER: PRJNA844003 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR19451420_1.fastq.gz	Fastqsanger.gz
	SRR19451420_2.fastq.gz	Fastqsanger.gz
	SRR19451421_1.fastq.gz	Fastqsanger.gz
	SRR19451421_2.fastq.gz	Fastqsanger.gz
	SRR19451422_1.fastq.gz	Fastqsanger.gz

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Neuropilin-2 regulates androgen-receptor transcriptional activity in advanced prostate cancer

Project description:Neuropilin-2 regulates androgen-receptor transcriptional activity in advanced prostate cancer

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Neuropilin-2 regulates androgen-receptor transcriptional activity in advanced prostate cancer [ChIP-seq]

Project description:Our study using prostate cancer tissues and cell lines observed that neuropilin-2 (NRP2) can translocate to the nucleus of advanced prostate cancer cells. NRP2 is present in the nuclear membrane and near to the nuclear pore. To understand the functions of nuclear NRP2 in prostate cancer, we have performed NRP2-specific chromatin immunoprecipitation DNA-sequencing (ChIP-seq) in prostate cancer cell. Our results showed NRP2 forms a complex with transcription factors and pore proteins, which helps the transcription factors to be recruited at the promoter regions of genes. The nature of the interaction between NRP2-transcription factors is dynamic and depends on various physiological and pathological conditions. The ChIP-seq was carried in duplicate using adenocarcinoma cell lines.

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Neuropilin-2 regulates androgen-receptor transcriptional activity in advanced prostate cancer [ChIP-seq]

Project description:Neuropilin-2 regulates androgen-receptor transcriptional activity in advanced prostate cancer [ChIP-seq]

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Neuropilin-2 regulates androgen-receptor transcriptional activity in advanced prostate cancer [RNA-seq]

Project description:Gene expression was first compared between control and NRP2 depletd condition in prostate adenocarcinoma cell line LNCaP C4-2B . In the next set, we compared the gene expression between control and AR deplted state in LNCaP C4-2B cells.

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The androgen receptor regulates a druggable translational regulon in advanced prostate cancer [ribosome profiling]

Project description:The recent advent of highly potent inhibitors of the androgen receptor and androgen biosynthesis has had the unfortunate iatrogenic effect of fueling new lethal prostate cancer phenotypes in patients. In particular, non-neuroendocrine androgen receptor-low castration resistant prostate cancer (AR low CRPC) is increasing in occurrence amongst patients and is uniformly fatal. The mechanisms that promote this phenotype remain poorly understood. Through molecular studies of murine and human models of AR low CRPC, we have identified a new functional interface between the androgen receptor and the translation initiation complex inhibitor 4EBP1. AR directly regulates 4EBP1 expression which translationally represses eIF4F complex formation and a pro-proliferation program. In the context of AR low prostate cancer, de-repression of translation initiation drives the aberrant expression of the pro-proliferation regulon which fuels uncontrolled cell growth. Genetic and pharmacologic inhibition of the downstream eIF4F translation initiation complex reverses the proliferation phenotype in vitro and in vivo. These findings reveal a new previously unrecognized druggable nexus which functionally link the processes of mRNA transcription and translation initiation in a rapidly emerging class of advanced lethal prostate cancer

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The androgen receptor regulates a druggable translational regulon in advanced prostate cancer [RNA-seq]

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Neuropilin-2 regulates androgen-receptor transcriptional activity in advanced prostate cancer.

Project description:Aberrant transcriptional activity of androgen receptor (AR) is one of the dominant mechanisms for developing of castration-resistant prostate cancer (CRPC). Analyzing AR-transcriptional complex related to CRPC is therefore important towards understanding the mechanism of therapy resistance. While studying its mechanism, we observed that a transmembrane protein called neuropilin-2 (NRP2) plays a contributory role in forming a novel AR-transcriptional complex containing nuclear pore proteins. Using immunogold electron microscopy, high-resolution confocal microscopy, chromatin immunoprecipitation, proteomics, and other biochemical techniques, we delineated the molecular mechanism of how a specific splice variant of NRP2 becomes sumoylated upon ligand stimulation and translocates to the inner nuclear membrane. This splice variant of NRP2 then stabilizes the complex between AR and nuclear pore proteins to promote CRPC specific gene expression. Both full-length and splice variants of AR have been identified in this specific transcriptional complex. In vitro cell line-based assays indicated that depletion of NRP2 not only destabilizes the AR-nuclear pore protein interaction but also inhibits the transcriptional activities of AR. Using an in vivo bone metastasis model, we showed that the inhibition of NRP2 led to the sensitization of CRPC cells toward established anti-AR therapies such as enzalutamide. Overall, our finding emphasize the importance of combinatorial inhibition of NRP2 and AR as an effective therapeutic strategy against treatment refractory prostate cancer.

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Transcriptional repression activity of androgen receptor targets cell plasticity in prostate cancer: BioID analysis

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Neuropilin-2 regulates androgen-receptor transcriptional activity in advanced prostate cancer

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

2022-06-03 | GSE205150 | GEO

The androgen receptor regulates a druggable translational regulon in advanced prostate cancer

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