Project description:We report the high-throughput profiling of AR binding in prostate cancer cells. Examination of AR binding in prostate cancer cell lines VCaP and VCS2
Project description:Here we used Illumina NGS for high-throughput profiling of the DNA methylome in seven human benign prostate tissues, seven human primary prostate cancer and six human castration resistant prostate cancer patient samples. These data were used to profile the CpG cytosine methylation pattern at single base resolution in each sample and to determine differentially methylated cytosines and regions among samples. Enhanced Reduced Representation Bisulfite Sequencing (ERRBS, MspI,150M-bM-^@M-^S400 bp size fractions) of 20 human prostate tissues (benign prostate tissues, localized and metastatic prostate cancer)
Project description:Prostate cancer is one of the major cancers that seriously affect men's health. It has high morbidity and high mortality, but there is still no ideal molecular markers for the diagnosis and prognosis of prostate cancer. Castration-resistant prostate cancer is associated with wide variations in survival. To determine whether differentially expressed circRNAs in plasma exosomes can be used as a novel biomarker for castration-resistant prostate cancer prognosis, we performed high-throughput circRNA sequencing on 15 pairs of plasma exosomes from 30 metastatic castration-resistant prostate cancer patients, with or without early progression, to screen differentially expressed circRNAs.
Project description:We report the application of ChIP sequencing technology for high-throughput profiling of H3K79me2 in prostate cancer cells. We generated genome-wide maps of LNCaP and PC3 cells that were treated with the specific DOT1L inhibitor EPZ004777. We find that lysine 79 dimethylation is sensitive to DOT1L inhibition in both cell lines, however the enrichment of K79 methylated peaks differed between the two cell lines.
Project description:Aggressive cancers and normal stem cells often share similar molecular and functional traits. It is unclear if aggressive phenotypes of prostate cancer molecularly resemble normal stem cells residing within the human prostate. We performed high-throughput RNA sequencing on uncultured, highly purified epithelial populations from human prostates obtained after radical prostatectomy. We found the basal population to be defined by genes associated with developmental programs, epigenetic remodeling, and invasiveness. We further generated a 91-gene basal signature and applied it to gene expression datasets from patients with organ-confined or castration-resistant, metastatic prostate cancer. Metastatic prostate cancer was more enriched for the basal stem cell signature than organ-confined prostate cancer. Moreover, histological subtypes within prostate cancer metastases varied in their enrichment of the stem cell signature with small cell neuroendocrine carcinoma being the most stem cell-like. Bioinformatic analysis of the basal cell and two human small cell gene signatures identified a set of E2F target genes common to all three signatures. These results suggest that the most aggressive variants of prostate cancer share a core transcriptional program with normal prostate basal stem cells. Transcriptional analysis of 10 uncultured prostatic basal and luminal populations from either the benign or malignant prostate tissue of 8 human prostate cancer patients by high-throughput RNA-seq
Project description:Background: Despite the significant global loss of DNA hydroxymethylation marks in prostate cancer tissues, the locus-specific role of hydroxymethylation in prostate tumorigenesis is unknown. We characterized hydroxymethylation and methylation marks by performing whole-genome next generation sequencing in representative normal and prostate cancer-derived cell lines in order to determine functional pathways and key genes regulated by these epigenomic modifications in cancer. Results: Our cell line model shows disruption of hydroxymethylation distribution in cancer, with global loss and highly specific gain in promoter and CpG island regions. Significantly, we observed locus-specific retention of hydroxymethylation marks in specific intronic and intergenic regions which may play a novel role in the regulation of gene expression in critical functional pathways, such as BARD1 signaling and steroid hormone receptor signaling in cancer. We confirm a modest correlation of hydroxymethylation with expression in intragenic regions in prostate cancer, while identifying an original role for intergenic hydroxymethylation in differentially expressed regulatory pathways in cancer. We also demonstrate a successful strategy for the identification and validation of key candidate genes from differentially regulated biological pathways in prostate cancer. Conclusion: Our results indicate a distinct function for aberrant hydroxymethylation within each genomic feature in cancer, suggesting a specific and complex role for the deregulation of hydroxymethylation in tumorigenesis, similar to methylation. Subsequently, our characterization of key cellular pathways exhibiting dynamic enrichment patterns for methylation and hydroxymethylation marks may allow us to identify differentially epigenetically modified target genes implicated in prostate cancer tumorigenesis. Methylation profiles of representative normal prostate cell line RWPE-1 and prostate adenocarcinoma cell line 22Rv1 were generated by MBD capture followed by high-throughput sequencing on the HiSeq 2500 (Illumina), in triplicate. Hydroxymethylation profiles of RWPE-1 and 22Rv1 were generated by hMeSeal followed by high-throughput sequencing on the HiSeq 2500 (one replicate each). Additional hydroxymethylation profiling for RWPE-1 was generated by hMeDIP followed by high-throughput sequencing on the HiSeq 2000 (Illumina).