ABSTRACT: To investigate if there is a difference of N6-methyladenosine(m6A) modification between castration-resistant prostate cancer (CRPC) and castration-sensitive prostate cancer (CSPC), we collected 30 specimens, including 15 CRPC and 15 CSPC, to perform RNA-seq and MeRIP-seq. All specimens were postoperative tissues and each 5 CRPC or CSPC specimens were mixed into 1 sample to meet the RNA dosage of RNA-seq and MeRIP-seq.
Project description:Acquisition of resistance to the PARP inhibitor, Olaparib, constitutes a major challenge for the treatment of advanced prostate cancer. The purpose of this study was to identify molecular targets responsible for the development of acquired Olaparib resistance in advanced prostate cancer. Towards this goal, next-generation sequencing (NGS)-based gene expression profiling (RNA-Sequencing; RNA-Seq) was performed on castration-sensitive prostate cancer (CSPC)/Olaparib-sensitive LNCaP cells, castration-sensitive prostate cancer (CSPC)/Olaparib-resistant LN-OlapR cells, castration-resistant prostate cancer (CSPC)/Olaparib-sensitive C4-2B cells, and castration-resistant prostate cancer (CSPC)/Olaparib-resistant 2B-OlapR cells.
Project description:PB-Cre/Pten/Smad4 is a transgenic mouse model of metastatic prostate adenocarcinoma (PMID: 21289624). To study the transcriptomic alterations associated with castration-resistant prostate cancer (CRPC), the PB-Cre/Pten/Smad4 males with established prostate cancer were treated with surgical castration followed by enzalutamide-admixed diet. After about 4 weeks, dorsolateral prostate (DLP) lobes of treatment-naïve prostate tumors (N=2) and CRPC tumors (N=3) were harvested and extracted for RNA purification and microarray profiling. To further study the transcriptomic changes associated with lung metastases of the PB-Cre/Pten/Smad4/mTmG CRPC model, the PB-Cre/Pten/Smad4 males with established prostate cancer were treated with surgical castration followed by enzalutamide-admixed diet. About 3 months later, from one mouse anterior prostate (AP), dorsolateral prostate (DLP), ventral prostate (VP) and GFP+ lung metastasis nodules were each harvested for RNA purification and microarray profiling.
Project description:To investigate the mechanisms underlying castration-resistant prostate cancer (CRPC) development, we used a prostate cancer (PCa) allograft mouse model. In this model, an androgen-dependent (AD) mouse prostate cancer cell line, Myc-CaP, was used. Myc-CaP cells can grow as primary prostate tumors (PPC) in immune competent FVB mice in an AD manner, when host mice are castrated, Myc-CaP allografts shrink (shrunken prostate tumor, S-PC), and later re-grow and become AR-positive CRPC. To compare the gene expression of different stage of PCa, primary cells from PPC, S-PC, and CRPC were isolated and purified. We used RNA-seq to detail the global programme of gene expression underlying castration-resistant prostate cancer (CRPC) development and identified distinct classes of up-regulated or down-regulated genes during this process.
Project description:We investigated the global OCT1 genomic signals using high-throughput chromatin immunoprecipitation sequencing (ChIP-seq) in a patient-derived model (PDX) of androgen receptor (AR)-negative or positive castration resistant prostate cancer (CRPC).
Project description:We generate transcription factor, histone modification and ATAC cistromes in castration-resistant prostate cancer (CRPC) and treatment-induced neuroendocrine prostate cancer (tNEPC) specimens.
Project description:Androgen receptor (AR) belongs to a nuclear receptor superfamily and functions as a ligand-dependent transcription factor. AR-regulated transcriptional program is associated with various diseases, especially prostate cancer. Suppression of AR is an effective therapy for AR-dependent prostate cancer. However, in most of the cases it relapses as castration-resistant prostate cancer (CRPC), acquiring resistance to hormone therapy. We investigated the effect of androgen treatment and AR knockdown on gene expression by RNA-seq using CRPC model cells.
Project description:The objective of this study is to identify gene signature associated with castration-refractory prostate cancer (CRPC) development. We carried out RNA-seq based transcriptome profiling using 45 prostate samples with various disease progression steps such as benign prostate hyperplasia (BPH), primary cancer of prostate (CaP), advanced CaP and CRPC. Via various statistical analyses, we identified significant gene set associated with each progression step and observed that AR was the only gene feature associated with all progression steps, indicating that AR is the crucial mediator of and has a diverse activity across the CaP progressions. Among the samples in this data set, there are 4 pairs of advanced CaP and CRPC samples, in which each pair was obtained from the same patient. Using these paired samples, we also determined differentially expressed genes between advanced CaP and CRPC, and performed comparative analysis of significant gene lists in matched sample pairs and in unpaired remained samples. By assessing expression difference between advanced CaP and CRPC groups, 309 and 182 genes were statistically significant in paired and unpaired samples, respectively (P < 0.001). When these two gene lists were compared, a total of 15 genes were common and applied to a number of downstream experimental assays.
Project description:Identifying biological change from hormone-naive prostate cancer to CRPC is a major clinical challenge for developing therapeutic agents. Although the pathways that lead to CRPC are not fully understood, recent evidence demonstrates that androgen signaling is often maintained through varied mechanisms. Here, we investigated PCa tissues at each stage of progression from benign prostatic hyperplasia (BPH) to CRPC based on quantitative proteomic technology, including tissues after ADT therapy. MS-based quantitative proteomics approach based on 6-plex TMT (126-131) was performed in patient tissues from T2G2 to CRPC, and benign prostatic hyperplasia (BPH) patient tissues were used as a control. We analyzed the peptide samples using two types of high resolution and accuracy mass spectrometers as LTQ orbitrap velos and Q-exactive mass spectrometer. In total, 4,768 proteins were identified in this study, among which 4,069 proteins were quantified in the combined prostate cancer tissues. Among the quantified proteins, DEPs were 865 (21.2%), those with a quantitative ratio greater than 2 were considered as upregulated, whereas those with a quantitative ratio of less than 0.5 as downregulated. Based on quantitative protein results, we performed systematic bioinformatics analysis including GO, Interpro, KEGG pathway, functional enrichment-based cluster analysis on DEPs. Finally, we found that 15 proteins including FOXA1 and HMGN1-3 between T3G3, T3GX, and CRPC were increased despite ADT treatment. Among all target, we verified increased level of FOXA1 and HMGN1-3 in CRPC by immunoblotting and indirect ELISA. In summary, we provides intracellular mechanical changes on PCa tissues according to treatment before and after ADT by mean of regulating ADT treatment. In addition, this results were identified through bioinformatics analysis, and those were suggested as potential CRPC-related factors.