Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

AR-V7 targets the oncogenic genes in castration resistant prostate cancer. [ChIP]

ABSTRACT: To elucidate the AR-V7 role, we performed ChIP-seq on H3K4me1, H3K4me3, H3K27ac, and AR antibody recognizing the N-terminus of AR and AR splice variants (AR-Vs) using LNCaP and LNCaP95 cells. We showed 399 AR-V7 targeted regions in LNCaP95, most of the AR-V7 target regions could be commonly activated by hormone stimulated AR. However, 22 regions were identified as AR-V7 specific regions. In addition, we show here that AR-V7 can transcript in the ligand independent manner in LNCaP95, unlike LNCaP. We identified the AR-V7 target gene contributing to the CRPC progression.

ORGANISM(S): Homo sapiens

PROVIDER: GSE122922 | GEO | 2020/11/02

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Androgen Receptor splice variant V7 (AR-V7) mediates AR signalling in castration resistant prostate cancer (CRPC) [ChIP-exo]

Project description:CRPC remains AR dependent. There are multiple mechanisms for reactivation of AR including expression of constitutively active AR splices variant AR-V7 (AR3). Earlier studies suggest that though the variants regulate many of the same genes as AR, they also have unique targets. Another argument is that the variant is a “weak” AR. We have used an LNCaP cell line that expresses AR-V7 in response to doxycycline to compare DNA interactions of the two isoforms and to identify differential regulation of target genes. ChIP-exo method was used to map AR and AR-V7 interaction with DNA in LNCaP engineered cell line (LNCaP AR-V7) at single base resolution.

2021-07-07 | GSE143906 | GEO

Androgen Receptor splice variant V7 (AR-V7) mediates AR signalling in castration resistant prostate cancer (CRPC) [RNA-seq]

Project description:CRPC remains AR dependent. There are multiple mechanisms for reactivation of AR including expression of constitutively active AR splices variant AR-V7 (AR3). Earlier studies suggest that though the variants regulate many of the same genes as AR, they also have unique targets. Another argument is that the variant is a “weak” AR. We have used an LNCaP cell line that expresses AR-V7 in response to doxycycline (LNCaP AR-V7) to compare the activities of the two isoforms and to identify differential regulation of target genes. We also used VCaP cell line that expresses AR-V7 in response to doxycycline (VCaP AR-V7) to validate the activities of the two isoforms in an alternative prostate cancer cell line. The transcriptomes for AR and AR-V7 in these cell lines were identified using RNA-Seq.

2021-01-21 | GSE143905 | GEO

Diverse AR-V7 cistromes in castration-resistant prostate cancer are governed by HoxB13

Project description:The constitutively active androgen receptor (AR) splice variant 7 (AR-V7) plays an important role in the progression of castration-resistant prostate cancer (CRPC). Although biomarker studies established the role of AR-V7 in resistance to AR-targeting therapies, how AR-V7 mediates genomic functions in CRPC remains largely unknown. Using a ChIP-exo approach, we show AR-V7 binds to distinct genomic regions and recognizes a full-length androgen-responsive element in CRPC cells and patient tissues. Remarkably, we find dramatic differences in AR-V7 cistromes across diverse CRPC cells and patient tissues, regulating different target gene sets involved in CRPC progression. Surprisingly, we discover that HoxB13 is universally required for and colocalizes with AR-V7 binding to open chromatin across CRPC genomes. HoxB13 pioneers AR-V7 binding through direct physical interaction, and collaborates with AR-V7 to up-regulate target oncogenes. Transcriptional coregulation by HoxB13 and AR-V7 was further supported by their coexpression in tumors and circulating tumor cells from CRPC patients. Importantly, HoxB13 silencing significantly decreases CRPC growth through inhibition of AR-V7 oncogenic function. These results identify HoxB13 as a pivotal upstream regulator of AR-V7-driven transcriptomes that are often cell context-dependent in CRPC, suggesting that HoxB13 may serve as a therapeutic target for AR-V7-driven prostate tumors.

2018-05-31 | GSE99378 | GEO

Transcriptome profiling of castration-resistant prostate cancer cells treated with novel androgen receptor (AR) and AR-V7 inhibitors

Project description:The purpose of this study was to characterize the downstream transcriptomic effects of ARVib-mediated degradation of AR/AR-V7, particularly in attenuating AR/AR-V7 target gene expression in prostate cancer cells. Towards this goal, next-generation sequencing (NGS)-based gene expression profiling (RNA-Sequencing; RNA-Seq) was performed on castration-resistant prostate cancer (CRPC) C4-2B MDVR cells that were treated with vehicle control or one of the AR/AR-V7 inhibitors (ARVib), ARVib-7 or ARVib-31.

2021-08-22 | GSE158556 | GEO

AR-V7 targets the oncogenic genes in castration resistant prostate cancer. [RNA]

Project description:To identify the AR-V7 target genes in human prostate cancer, two cell lines (LNCaP, LNCaP95) were subjected to RNA-seq analysis.

2020-11-02 | GSE122923 | GEO

Spermine is a natural suppressor of AR signaling in castration-resistant prostate cancer

Project description:In castration-resistant prostate cancer (CRPC), clinical response to androgen receptor (AR) antagonists is limited mainly due to AR-variants expression and restored AR signaling. The metabolite spermine is most abundant in prostate and it decreases as prostate cancer progresses, but its functions remain poorly understood. Here, we show spermine inhibits full-length androgen receptor (AR-FL) and androgen receptor splice variant 7 (AR-V7) signaling and suppresses CRPC cell proliferation by directly binding and inhibiting protein arginine methyltransferase PRMT1. Spermine reduces H4R3me2a modification at the AR locus and suppresses AR binding as well as H3K27ac modification levels at AR target genes. Spermine supplementation restrains CRPC growth in vivo. PRMT1 inhibition also suppresses AR-FL and AR-V7 signaling and reduces CRPC growth. Collectively, we demonstrate spermine as an anticancer metabolite by inhibiting PRMT1 to transcriptionally inhibit AR-FL and AR-V7 signaling in CRPC, and we indicate spermine and PRMT1 inhibition as powerful strategies overcoming limitations of current AR-based therapies in CRPC.

2023-10-11 | MTBLS8034 | MetaboLights

Role of androgen receptor splice variant 7 (AR-v7) in prostate cancer resistance to 2nd generation androgen receptor signaling inhibitors

Project description:Since its discovery, there has been one central issue of significant clinical relevance related to expression of the truncated androgen receptor splice variant-7 (AR-v7), which lacks the C-terminal ligand binding domain and thus acquires ligand-independent transcriptional activity in castration-resistant prostate cancer (CRPC). That question is whether AR-v7 is simply a marker of enhanced AR transcriptional activity characteristic of resistance to 2nd generation androgen receptor signaling inhibitors (ARSi) like Abiraterone and Enzalutamide, or whether it drives lethal resistance to ARSi. To address this question, the present study utilized 4 independently derived CRPC patient-derived xenografts in which the genetic and phenotypic changes could be followed before and after the development of ARSi resistance. This allowed evaluation of the correlation between acquired resistance to ARSi and changes in the expression levels of full length AR (AR-FL) vs. AR-v7 during this process. The combined results document that elevated expression of AR-FL alone is sufficient for Abiraterone- but not Enzalutamide-resistance. This is true even if AR-FL has a gain-of-function mutation. Furthermore, Enzalutamide-resistance is consistently correlated with the acquisition of AR-v7 expression. To directly test the requirement for AR-v7 expression in ARSi-refractory CRPC, CRISPR-Cas9 knockout of AR-FL and/or AR-v7 in LNCaP-95 cells was performed to evaluate in vitro and in vivo growth responses. These results document that AR-v7 drives Enzalutamide-resistance and focuses the critical need to develop therapeutic options to prevent and/or inhibit AR-v7 driven lethal progression of CRPC.

2020-10-11 | GSE149433 | GEO

Heterogeneity of Androgen Receptor Splice Variant-7 (AR-V7) Protein Expression and Response to Therapy in Castration Resistant Prostate Cancer (CRPC)

Project description:Liquid biopsies have demonstrated that the constitutively active androgen receptor splice variant-7 (AR-V7) associates with reduced response and overall survival (OS) from endocrine therapies in castration resistant prostate cancer (CRPC). However, these studies provide little information pertaining to AR-V7 biology and expression in prostate cancer (PC) tissue. Following generation and validation of a novel AR-V7 antibody for immunohistochemistry (IHC); nuclear AR-V7 protein expression was determined for 358 primary prostate samples (358 patients) and 293 metastatic biopsies (194 patients). Associations with disease progression, nuclear AR full length (AR-FL) expression, response to abiraterone and/or enzalutamide, and gene signatures (from three independent cohorts) was determined.

2018-10-19 | GSE118435 | GEO

Androgen Receptor splice variant V7 (AR-V7) mediates AR signalling in castration resistant prostate cancer (CRPC)

Project description:Androgen Receptor splice variant V7 (AR-V7) mediates AR signalling in castration resistant prostate cancer (CRPC)

| PRJNA602078 | ENA

Transcriptome profiling of castration resistant prostate cancer cells treated with novel AR N-terminal inhibitor

Project description:This study aimed at exploring how would the novel AR N-terminal inhibitor affect the androgen receptor (AR) transcriptome, especially a subset of genes that are uniquely upregulated by AR-V7 in castration resistant prostate cancer cells. We performed next-generation sequencing-based gene expression profiling (RNA-sequencing) on the castration-resistant prostate cancer celll line LNCaP-95. LNCaP-95 expresses high level of endogeneous AR-V7, and also acquired an adaptive shift towards AR-V7-mediated AR signaling activity. Beside regulating the transcription of a subset of canonical wildtype AR genes, AR-V7 also mediates a distinct transcriptional program that is independent of wildtype AR in LNCaP-95. In this experiment, LNCaP-95 cells were treated with vehicle control or the AR-N terminal inhibitor SC912. The subsequent AR transcriptomic change following compound treatment, especially the AR-V7 unique genes were assessed by RNA-seq.

2024-04-30 | GSE253122 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data