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PROVIDER: PRJNA491402 | ENA |
REPOSITORIES: ENA
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Project description:Genomic Analysis of DNA Repair Genes and Androgen Signaling in Prostate Cancer
| PRJNA493954 | ENA
Project description:Abstract Background. The cellular effects of androgen are transduced through the androgen receptor, which controls the expression of genes that regulate biosynthetic processes, cell growth, and metabolism. Androgen signaling also impacts DNA damage signaling through mechanisms involving gene expression and transcription-associated DNA damaging events. Defining the contributions of androgen signaling to DNA repair is important for understanding androgen receptor function, and it also has important translational implications. Methods. We generated RNA-seq data from multiple prostate cancer lines and used bioinformatic analyses to characterize androgen-regulated gene expression. We compared the results from cell lines with gene expression data from prostate cancer xenografts, and patient samples, to query how androgen signaling and prostate cancer progression influences the expression of DNA repair genes. We performed whole genome sequencing to help characterize the status of the DNA repair machinery in widely used prostate cancer lines. Finally, we tested a DNA repair enzyme inhibitor for effects on androgen-dependent transcription. Results. Our data indicates that androgen signaling regulates a subset of DNA repair genes that are largely specific to the respective model system and disease state. We identified deleterious mutations in the DNA repair genes RAD50 and CHEK2. We found that inhibition of the DNA repair enzyme MRE11 with the small molecule mirin inhibits androgen-dependent transcription and growth of prostate cancer cells. Conclusions. Our data supports the view that crosstalk between androgen signaling and DNA repair occurs at multiple levels, and that DNA repair enzymes in addition to PARPs, could be actionable targets in prostate cancer.
2018-09-30 | GSE120660 | GEO
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
Project description:Prostate cancer is the most common cancer in men and AR downstream signalings promote prostate cancer cell proliferation. We identified androgen-regulated long non-coding RNA, CTBP1-AS, located in the antisese region of CTBP1 gene. CTBP1-AS activate AR signaling by epigenetically repress AR-associated cofactors such as CTBP1 by interactign with RNA-binding protein PSF and recruiting HDAC complex to the target promoters. In order investigated the PSF target genes, we performed ChIP-seq analysis of PSF binding sites in prostate cancer cell line, LNCaP cells. We identified androgen dependent PSF binding regions in prostate cancer cell genome. We observed PSF bindings around the promoters of androgen repressed genes such as CTBP1, p53 and SMAD3. ChIP-sequence analysis of PSF binding sites in prostate cancer cells
2014-01-01 | E-GEOD-45124 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE30622: Dual Role of FoxA1 in Androgen Receptor Binding to Chromatin, Androgen Signaling and Prostate Cancer [Expression Array] GSE30623: Dual Role of FoxA1 in Androgen Receptor Binding to Chromatin, Androgen Signaling and Prostate Cancer [ChIP_seq, DHS_seq] Refer to individual Series
2011-09-13 | E-GEOD-30624 | biostudies-arrayexpress
Project description:Prostate cancer is the most common cancer in men and AR downstream signalings promote prostate cancer cell proliferation. To investigate the AR signaling, we performed ChIP sequence analysis in AR positive prostate cancer cell line, LNCaP. In addition, we used hormone-refractory prostate cancer model cells, Bicalutamide-resistant (BicR) to explore the differences of androgen signaling in prostate cancer progression. ChIP sequence analysis of AR binding sites and epigenetic condition in two prostate cancer cells
2015-09-01 | E-GEOD-66037 | biostudies-arrayexpress
Project description:Prostate cancer is the most common cancer in men and AR downstream signalings promote prostate cancer cell proliferation. To investigate the AR signaling, we performed ChIP sequence analysis in AR positive prostate cancer cell line, LNCaP and VCaP. In addition, we used hormone-refractory prostate cancer model cells, long term androgen deprivation (LTAD) to explore the differences of androgen signaling in prostate cancer progression.
2018-04-23 | GSE94577 | GEO
Project description:Prostate cancer is the second most occurring cancer in men worldwide, and with the advances made with screening for prostate-specific antigen, it has been prone to early diagnosis and over-treatment. To better understand the mechanisms of tumorigenesis and possible treatment responses, we developed a mathematical model of prostate cancer which considers the major signalling pathways known to be deregulated. The model includes pathways such as androgen receptor, MAPK, Wnt, NFkB, PI3K/AKT, MAPK, mTOR, SHH, the cell cycle, the epithelial-mesenchymal transition (EMT), apoptosis and DNA damage pathways. The final model accounts for 133 nodes and 449 edges. We applied a methodology to personalise this Boolean model to molecular data to reflect the heterogeneity and specific response to perturbations of cancer patients, using TCGA and GDSC datasets.
2022-06-22 | MODEL2106070001 | BioModels
Project description:Prostate cancer is the most common cancer in men and AR downstream signalings promote prostate cancer cell proliferation. To investigate the AR signaling, we performed CaP analysis of gene expression (CAGE) analysis in AR positive prostate cancer cell line, LNCaP. In addition, we used hormone-refractory prostate cancer model cells, Bicalutamide-resistant (BicR) to explore the differences of androgen signaling in prostate cancer progression. CAGE analysis of androgen-regulated transcripts in two prostate cancer cells
2015-09-01 | E-GEOD-66034 | biostudies-arrayexpress
Project description:Prostate cancer is the most common cancer in men and AR downstream signalings promote prostate cancer cell proliferation. To investigate the AR signaling, we performed RNA sequence analysis in AR positive prostate cancer cell line, LNCaP. In addition, we used hormone-refractory prostate cancer model cells, Bicalutamide-resistant (BicR) to explore the differences of androgen signaling in prostate cancer progression. Short RNA sequence analysis of androgen-regulated miRNAs in two prostate cancer cells
2015-09-01 | E-GEOD-66036 | biostudies-arrayexpress