Project description:Effects of sulforaphane and 3,3’-diindolylmethane on genome-wide promoter methylation in normal prostate epithelial cells and prostate cancer cells This study was undertaken to determine the genome-wide effects of sulforaphane (SFN) and 3,3’-diindolylmethane (DIM) on promoter methylation in normal prostate epithelial cells and prostate cancer cells. Nimblegen Human DNA Methylation 3x720K CpG Island Plus RefSeq Promoter Array was used in this study. We hypothesize that both SFN and DIM are effective dietary modulators of DNA methylation due to their inhibitory effects on DNMT expression, and that SFN and DIM can differentially affect the promoter methylation profiles in normal and cancerous prostate epithelial cells.
Project description:Effects of sulforaphane and 3,3’-diindolylmethane on genome-wide promoter methylation in normal prostate epithelial cells and prostate cancer cells This study was undertaken to determine the genome-wide effects of sulforaphane (SFN) and 3,3’-diindolylmethane (DIM) on promoter methylation in normal prostate epithelial cells and prostate cancer cells. Nimblegen Human DNA Methylation 3x720K CpG Island Plus RefSeq Promoter Array was used in this study. We hypothesize that both SFN and DIM are effective dietary modulators of DNA methylation due to their inhibitory effects on DNMT expression, and that SFN and DIM can differentially affect the promoter methylation profiles in normal and cancerous prostate epithelial cells. Normal prostate epithelial cells (PrEC), androgen-dependent prostate cancer epithelial cells (LnCAP) and androgen-independent prostate cancer epithelial cells (PC3) were treated with vehicle control, 15uM SFN, or 15uM DIM for 48h in triplicates
Project description:Epidemiological studies provide strong evidence that consumption of cruciferous vegetables, such as broccoli, can significantly reduce the risk of developing cancers. Sulforaphane (SFN), a phytochemical derived from cruciferous vegetables, induces anti-proliferative and pro-apoptotic responses in prostate cancer cells, but not in normal prostate cells. The mechanisms responsible for these specific chemopreventive properties remain unclear. We utilized RNA sequencing to test the hypothesis that SFN modifies the expression of genes that are critical in prostate cancer progression. Normal prostate epithelial cells, and androgen-dependent and androgen-independent prostate cancer cells were treated with 15 µM SFN and the transcriptome was determined at 6 and 24 hour time points. SFN altered the expression of ~3,000 genes in each cell line and the response was highly dynamic over time. SFN influenced the expression of genes in functional groups and pathways that are critical in cancer including cell cycle, apoptosis and angiogenesis, but the specific effects of SFN differed depending on the state of cancer progression. Network analysis suggested that a transcription factor that is overexpressed in many cancers, Specificity protein 1 (Sp1), is a major mediator of SFN-induced changes in gene expression. Nuclear Sp1 protein was significantly decreased by 24 hour SFN treatment in prostate cancer cells, while a related transcription factor, Sp3 protein was only modestly decreased in androgen-independent prostate cancer cells. Overall, the data show that SFN significantly affects gene expression in normal and cancer cells, with key targets in chemopreventive processes, making it a promising dietary anti-cancer agent. Examination of how the transcriptome of normal and prostate cancer cells is altered by treatment with sulforaphane
Project description:Epidemiological studies provide strong evidence that consumption of cruciferous vegetables, such as broccoli, can significantly reduce the risk of developing cancers. Sulforaphane (SFN), a phytochemical derived from cruciferous vegetables, induces anti-proliferative and pro-apoptotic responses in prostate cancer cells, but not in normal prostate cells. The mechanisms responsible for these specific chemopreventive properties remain unclear. We utilized RNA sequencing to test the hypothesis that SFN modifies the expression of genes that are critical in prostate cancer progression. Normal prostate epithelial cells, and androgen-dependent and androgen-independent prostate cancer cells were treated with 15 µM SFN and the transcriptome was determined at 6 and 24 hour time points. SFN altered the expression of ~3,000 genes in each cell line and the response was highly dynamic over time. SFN influenced the expression of genes in functional groups and pathways that are critical in cancer including cell cycle, apoptosis and angiogenesis, but the specific effects of SFN differed depending on the state of cancer progression. Network analysis suggested that a transcription factor that is overexpressed in many cancers, Specificity protein 1 (Sp1), is a major mediator of SFN-induced changes in gene expression. Nuclear Sp1 protein was significantly decreased by 24 hour SFN treatment in prostate cancer cells, while a related transcription factor, Sp3 protein was only modestly decreased in androgen-independent prostate cancer cells. Overall, the data show that SFN significantly affects gene expression in normal and cancer cells, with key targets in chemopreventive processes, making it a promising dietary anti-cancer agent.
Project description:To identify new oncogenic drivers in prostate cancer, we performed transcriptome analysis of localized primary prostate cancer samples and the matched normal tissues.
Project description:LINC00920 is a tumor-associated lncRNA identified in the transcriptome dataset of the International Cancer Genome Consortium-Early Onset Prostate Cancer (ICGC-EOPC) cohort. SiRNA-mediated knockdown of LINC00920 negatively affected proliferation, colony formation, and migration of PC-3 prostate cancer cells. Genome-wide expression profiling was performed to identify cellular pathways affected by LINC00920.
Project description:DNA methylation plays a key role in demarcation of regulatory regions, including promoter-associated CpG islands. While CpG islands are typically maintained in an unmethylated state in normal cells, a proportion of CpG islands are subject to hypermethylation in cancer cells. It still remains elusive how the exquisite demarcation of the bimodal methylation state is established and maintained at the CpG island flanks and conversely what triggers the erosion of CpG island DNA methylation in tumorigenesis. Here, we applied whole-genome bisulphite sequencing to study the comprehensive methylation patterns of prostate normal and cancer tissues. Alongside we performed TET-assisted bisulphite sequencing to study genome-wide DNA hydroxymethylation patterns of normal prostate and prostate cancer tissues.
Project description:DNA methylation plays a key role in demarcation of regulatory regions, including promoter-associated CpG islands. While CpG islands are typically maintained in an unmethylated state in normal cells, a proportion of CpG islands are subject to hypermethylation in cancer cells. It still remains elusive how the exquisite demarcation of the bimodal methylation state is established and maintained at the CpG island flanks and conversely what triggers the erosion of CpG island DNA methylation in tumorigenesis. Here, we applied whole-genome bisulphite sequencing to study the comprehensive methylation patterns of prostate normal and cancer tissues. Alongside we performed TET-assisted bisulphite sequencing to study genome-wide DNA hydroxymethylation patterns of normal prostate and prostate cancer tissues.