Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1088714 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR28389055_1.fastq.gz | Fastqsanger.gz | |||
| SRR28389055_2.fastq.gz | Fastqsanger.gz | |||
| SRR28389056_1.fastq.gz | Fastqsanger.gz | |||
| SRR28389056_2.fastq.gz | Fastqsanger.gz | |||
| SRR28389057_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 24 |
Similar Datasets
Project description:The androgen receptor (AR) is a therapeutic target of prostate cancer (PCa). Targeted AR therapy commonly uses androgen deprivation therapy (ADT) and AR antagonists to reduce androgen levels and inhibit tumor growth. Surprisingly, treatment with supraphysiological androgen level (SAL) can also inhibit the growth of PCa. SAL (R1881) was shown to induce cellular senescence in PCa. Knockdown of BHLHE40 in C4-2 and LNCaP cell lines indicates that BHLHE40 mediates SAL-induced cellular senescence as a possible tumor suppressive pathway. The RNA-seq from BHLHE40 knocked down C4-2 cells confirmed that BHLHE40 regulates cellular senescence and associated pathways. Interestingly, a large overlap of differentially expressed gene sets was identified between BHLHE40 regulated transcriptome and the SAL-changed transcriptome leading to four classes of up-and downregulated BHLHE40 transcriptome landscapes overlapping with that of AR. Further RNA-seq analyses revealed that the tumor suppressive cyclin G2 (CCNG2) emerged as a novel downstream target of BHLHE40. Knockdown of CCNG2 suggests that it mediates SAL-induced cellular senescence providing evidence of a novel pathway by the AR-BHLHE40-CCNG2 axis to mediate androgen-induced cellular senescence as a novel tumor suppressive pathway in PCa cells.
2024-06-21 | GSE262117 | GEO
Project description:The bipolar androgen therapy (BAT) to treat prostate cancer includes cycles of supraphysiological androgen levels (SAL) under continuous androgen deprivation therapy (ADT). We showed previously that SAL induces cellular senescence in androgen-sensitive PCa cells and ex vivo in PCa tumor samples from patients that underwent radical prostatectomy. Here, we show that SAL induces cellular senescence in both, castration sensitive (CSPC) LNCaP and castration resistant PCa (CRPC) C4-2 cells through the cell cycle inhibitor p15. Treatment with the Akt inhibitor (Akti) potently inhibited SAL-induced expression of p15 and cellular senescence in both cell lines. Proximity ligation assays (PLA) combined with high-resolution laser-scanning microscopy indicate that SAL promotes interaction of endogenous androgen receptor (AR) with endogenous Akt in cytoplasm as well as in nucleus after 72 hours hormone treatment. This suggests that the AR interacts with Akt also in a long-term manner. Transcriptome sequencing (RNA-seq) comparing the SAL-induced transcriptomes of LNCaP with C4-2 cells as well as of Akti treated cells revealed landscapes for cell senescence. Interestingly, one of the identified genes is the lncRNASAT1. SAL treatment of native patient tumor samples ex vivo results in upregulation of lncRNASAT1. The lncRNASAT1 is down-regulated in PCa tumor tissues compared to non-tumor tissues of same patients indicating a tumor suppressive function. Knockdown indicates that the lncRNASAT1 is crucial for SAL-induced cancer cell senescence and regulates LNCaP cell proliferation being an upstream factor for pAkt and for p15. Further, knockdown of lncRNASAT1 inhibits LNCaP cell proliferation by low androgen levels but enhances proliferation by SAL. This suggests that lncRNASAT1 serves as a tumor suppressor with SAL. Interestingly, immunoprecipitation of AR detected lncRNASAT1 as an AR interacting partner that regulates AR target gene expression. Thus, we identified a novel pathway of androgen signaling as the AR- lncRNASAT1- Akt- p15INK4b- axis to mediate SAL-induced cellular senescence.
2022-03-04 | GSE162711 | GEO
Project description:Castration-resistant prostate cancer (CRPC) is an incurable form of prostate cancer (PC) and a major therapeutic challenge. Here, we show that the natural compound, atraric acid (AA), inhibits besides the androgen receptor (AR) those AR-mutants that confer therapy resistance to AR-antagonists indicating a different mode of AR-antagonism. AA induces cellular senescence and inhibits intratumoral angiogenesis and CRPC tumour growth in treated xenograft mice. RNA-seq reveals an upregulated angiogenic transcriptional pathway by androgen. In line with this, conditioned medium from CRPC cells induces angiogenesis in two in vitro models using primary human endothelial cells. By employing immune arrays and mass-spec analyses, we found that androgens induced secretion of pro-angiogenic factors pinpointing to angiopoeitin2 (ANGPT2). The senescence-associated secretory phenotype revealed reduced ANGPT2 secretion by AA. Accordingly, immune-depletion of ANGPT2 or blocking ANGPT2-receptors inhibits angiogenesis. Our data propose AA as potential anti-PCa compound and ANGPT2 pathway as novel therapeutic target for CRPC.
2021-08-31 | GSE151492 | GEO
Project description:Long noncoding RNAs (lncRNAs) have recently been associated with the development and progression of a variety of human cancers. However, to date, the interplay between known oncogenic or tumor suppressive events and lncRNAs has not been well described. Here the novel lncRNA, Prostate Cancer-Associated Transcript 29 (PCAT29), is characterized along with its relationship to the androgen receptor (AR). PCAT29 is suppressed by dihydrotestosterone (DHT) and up-regulated upon castration therapy in a prostate cancer xenograft model. PCAT29 knockdown significantly increased proliferation and migration of prostate cancer cells, while PCAT29 overexpression conferred the opposite effect and suppressed growth and metastases of prostate tumors in chick chorioallantoic membrane (CAM) assays. Finally, in prostate cancer patient specimens, low PCAT29 expression correlated with poor prognostic outcomes. Taken together, these data expose PCAT29 as an androgen regulated tumor suppressor in prostate cancer PCAT29 was knockdown using shRNA in two prostate cancer cell lines VCaP and LNCaP.
2014-07-01 | E-GEOD-58397 | biostudies-arrayexpress
Project description:Orthotopic tumors were previously generated from parental Prostate Luminal (PLum) cells under androgen‑dependent (PLum-AD) and androgen‑independent (PLum-AI) conditions in order to establish cellular models of prostate cancer progression (Abou-Kheir et al., 2011; doi: 10.1371/journal.pone.0026112). We used microarrays to evaluate the differential gene expression profiles underlying progression of prostate cancer from primary androgen-dependent stage to advanced androgen-independent stage using newly isolated murine prostate cancer cell lines. Those cell lines represent novel in vitro models of androgen‑dependent and –independent prostate cancer, recapitulating the progression of the disease to a more invasive phenotype upon androgen deprivation.
2020-05-27 | GSE151187 | GEO
Project description:The androgen receptor-lncRNASAT1-Akt-p15 axis mediates androgen-induced cellular senescence in prostate cancer cells
| PRJNA682650 | ENA
Project description:Androgen receptor (AR) signalling pathway plays an important role in carcinogenesis and development of prostate cancer. The involvement of microRNA (miRNA) in this process is still largely unknown. In this study, we performed a matched miRNA-mRNA time-course expression profiling to reveal androgen response in hormone-sensitive prostate cancer cells.We introduced novel statistics Response Score (RS) and Modulation Score (MS) to identify significant androgen-regulated target genes and miRNA-modulated target mRNAs. Based on the analysis, we found several novel androgen-regulated targets, which had significant androgen response in expression pattern, and were highly enriched in predicted androgen responsive elements (AREs). AR-bindings to these AREs were validated with ChIP assay. Furthermore, a set of target mRNAs involved in crucial processes of tumor progression were identified to be significantly regulated by these miRNAs. Therefore, a miRNA-mediated androgen signalling network was inferred, including three novel feedback mechanisms for AR self-modulation. In conclusion, our study provides new approaches to further miRNA regulation research and contributes novel findings into miRNA-mediated pathological effects in prostate cancer. Total RNA obtained from androgen dihydrotestosterone (DHT) subjected to LNCaP cells in vitro at 20min, 40min, 1h, 2h, 4h, 8h, 16h, 24h and 48h, compared to the control at 0h.
2011-12-31 | E-GEOD-21245 | biostudies-arrayexpress
Project description:We report the high-throughput profiling of histone modifications in prostate cancer cells. By obtaining over 1 billion bases of sequence from chromatin immunoprecipitated DNA, we generated genome-wide chromatin-state maps of prostate cancer cells. we found androgen treatment dismisses a nucleosome over AR binding sites that are flanked by a pair of H3K4me2 marked nucleosomes. A novel quantitative model built on the behavior of such nucleosome pairs correctly identified regions bound by the regulators of the immediate androgen response including AR and FoxA1. More importantly this model also correctly predicted novel binding sites for other transcription factors present following prolonged androgen stimulation including Oct1 and NKX3.1. Thus quantitative modeling of enhancer structure provides a powerful predictive method to infer the identity of transcription factors involved in cellular responses to specific stimuli. Examination of 2 different histone modifications in prostate cancer cells with and without androgen (dihydrotestosterone, DHT) treatment.
2010-03-09 | E-GEOD-20042 | biostudies-arrayexpress
Project description:Castration‑resistant prostate cancer (CRPC) is an aggressive lethal form of prostate cancer (PCa), which presents a major therapeutic challenge. Here, we show that the natural compound, atraric acid (AA), inhibits not only the androgen receptor (AR) but also targets those AR-mutants that confer therapy resistance to other clinically used AR-antagonists indicating a different mode of AR-antagonism. AA induces cellular senescence in CRPC and inhibits CRPC tumour growth in vivo xenograft model. The secretome of CRPC cells induces androgen-dependent angiogenesis, which is counteracted by AA regulated senescence-associated secretory phenotype (SASP) in two in vitro models using primary human endothelial cells. In line with this, in tumours, vessel number is decreased in the mouse group treated with AA suggesting the repression of intratumoural neo-angiogenesis by AA. Transcriptome sequencing and mass spec analysis of the secretome revealed upregulated angiogenic pathways by androgen, however, being VEGF-independent and pointing to the secretion of the pro-angiogenic factor angiopoietin 2 (ANGPT2) induced by androgens and repressed by AA as a key driver of neo-angiogenesis. In agreement with this, AA treatment of native patient-derived PCa tumour samples ex vivo inhibits ANGPT2 expression. Mechanistically, besides AA, immune-depletion of ANGPT2 or blocking ANGPT2-receptors inhibits androgen-induced angiogenesis. Taken together, we reveal a VEGF-independent ANGPT2 pathway targeted by AA to inhibit androgen-regulated neo-angiogenesis.
2022-06-23 | GSE172205 | GEO
Project description:Cellular senescence, a stable cell growth arrest, can have dual effects in tumors, either suppressing or promoting tumor progression. The Senescence-Associated Secretory Phenotype (SASP), released by senescent cells, plays a crucial role in this dichotomy. Consequently, the clinical challenge lies in developing therapies that safely enhance senescence in cancer, promoting tumor-suppressive over tumor-promoting SASP factors. Here, we identified the Retinoic-Acid-Receptor (RAR) agonist Adapalene as an effective pro-senescence compound in prostate cancer (PCa). The reactivation of the RARs triggers a strong senescence response and a tumor-suppressive SASP. In preclinical mouse models of PCa, the combination of Adapalene and Docetaxel, promotes a tumor-suppressive SASP that activates NK cell-mediated tumor clearance more effectively than either agent alone. This approach increases the efficacy of allogenic infusion of human NK cells in mice injected with human PCa cells, suggesting an alternative therapeutic strategy to stimulate the anti-tumor immune response in "immunologically cold" tumors.
2024-02-29 | GSE253331 | GEO