Transcriptome analyses of AR-V7 and ARv567es
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ABSTRACT:
PROVIDER: PRJNA913105 | ENA |
REPOSITORIES: ENA
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Project description:Although AR-V7 has been intensively studied, it remains unclear whether AR-V7 and other AR splicing variants can specifically activate a distinctive transcriptional program from the full-length AR (AR-FL), and whether AR-V7 may play a role in accelerating the metastatic progression of castration-resistant PCa (CRPC). In this study, we hypothesize that AR-V7 can drive a distinct transcription program from AR-FL in CRPC condition. To test this, we used LNCaP model with inducible overexpression of AR-V7 or AR-V7-S81A to examine the transcriptional function of AR-V7 and the role of S81 phosphorylation on AR-V7 transcriptome. We also studied the endogenous AR-V7 transcriptome in CWR-22Rv1 cells using siRNA against AR-V7. Lastly, we used LNCaP model with inducible overexpression of AR-V567es to examine the AR-V567es transcriptome.
2024-06-05 | GSE221141 | GEO
Project description:Although AR-V7 has been intensively studied, it remains unclear whether AR-V7 can specifically activate a distinctive transcriptional program from the full-length AR (AR-FL), and whether AR-V7 may play a role in accelerating the metastatic progression of castration-resistant PCa (CRPC). In this study, we hypothesize that AR-V7 can drive a distinct transcription program from AR-FL in CRPC condition. To test this, we used LNCaP model with inducible overexpression of AR-V7 or AR-FL to examine the effects of AR-V7 overexpression or AR-FL overexpression stimulated with DHT for 4 hours on AR-V7 or AR-FL cistromes. We also studied the effects of AR-V7 on cistromes of pioneer factor FOXA1 and active histone marker H3K27ac, and the function of phosphorylation at Ser81 on AR-V7 function in CRPC.
2024-06-05 | GSE221140 | GEO
Project description:Although AR-V7 has been intensively studied, it remains unclear whether AR-V7 and other AR splicing variants can specifically activate a distinctive transcriptional program from the full-length AR (AR-FL), and whether AR-V7 may play a role in accelerating the metastatic progression of castration-resistant PCa (CRPC). In this study, we hypothesize that AR-V7 can drive a distinct transcription program from AR-FL in CRPC condition. To test this, we performed ATAC-seq using LNCaP model with inducible overexpression of AR-V7 to examine the function of AR-V7. We demonstrated that AR-V7 has “pioneer factor-like” activities to access the androgen-responsive elements (AREs) located at compact chromatin regions. More importantly, we found that SOX9, a critical metastasis driver gene, was a direct target and downstream effector of AR-V7, and its protein expression was dramatically upregulated at AR-V7-induced bone lesions.
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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.
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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
Project description: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.
2020-11-02 | GSE122922 | GEO
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
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.
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