Project description:Genome-wide DNA methylation profiling of human PC3 invasive prostate cancer cell line treated with vehicle control (SAH, S-adenosylhomocysteine) and with SAM (S-adenosylmethionine) as well as of untreated human LNCaP non-invasive prostate cancer cell line. The Illumina Infinium 450k Human DNA Methylation BeadChip v1.2 was used to obtain DNA methylation profiles across approximately 450,000 CpGs in human cell lines exposed to described treatments. Samples included biological triplicate of PC3 control (SAH treated), biological triplicate of PC3 treated with SAM, and biological duplicate of LNCaP untreated.
Project description:Genome-wide DNA methylation profiling of human PC3 invasive prostate cancer cell line treated with vehicle control (SAH, S-adenosylhomocysteine) and with SAM (S-adenosylmethionine) as well as of untreated human LNCaP non-invasive prostate cancer cell line. The Illumina Infinium 450k Human DNA Methylation BeadChip v1.2 was used to obtain DNA methylation profiles across approximately 450,000 CpGs in human cell lines exposed to described treatments. Samples included biological triplicate of PC3 control (SAH treated), biological triplicate of PC3 treated with SAM, and biological duplicate of LNCaP untreated. Bisulfite-converted DNA from the 8 samples were hybridised to the Illumina Infinium 450k Human Methylation BeadChip v1.2.
Project description:S-adenosylmethionine represents a potent inhibitor of cancer cell proliferation, migration and invasion in vitro. The reason remains unclear. Here, we examined if treatment with exogenous SAM is capable of causing alterations in the methylation of the histone markers H3K4me3 and H3K27me3, which are both known to be important in the initiation and progression of prostate cancer.
Project description:Neuroendocrine transdifferentiation (NED) of prostate cancer cells and aberrant activation of survival pathways involved in tumorigenesis are among the events that lead to the development of resistance to anti-androgen therapy and are associated with poor prognosis in patients with castration resistance prostate cancer (CRPC). Most of these molecular events appear to be mediated by epigenetic mechanisms, in particular DNA methylation. In this study, we evaluated the antitumor activity and epigenetic modulation of two epigenetic drugs, 5-aza-2’-deoxycytidine (AZA) and S-adenosylmethionine (SAM) in two human CRPC cell lines with NED (NED-CRPC), DU-145 and PC-3. The effects of AZA and SAM on the cell growth proliferation, cell cycle, apoptosis, migration and genome-wide DNA methylation profiling have been evaluated through MTT assay, DNA flow cytometry with propidium iodide, and Annexin V-FITC/propidium iodide staining, wound-healing assay and Infinium450k microarray, respectively. Both epigenetic drugs showed a prominent antitumor activity in NED-CRPC cell line exerted through perturbation of cell cycle progression, induction of apoptosis and migration arrest. AZA and SAM reversed NED in DU-145 and PC-3, respectively. Moreover, AZA treatment profoundly modified DNA methylation pattern, sustaining a pervasive hypomethylation of the genome, with a relevant effect on several pathways involved in regulation of cell migration, cell proliferation and apoptosis. Among these, the Wnt/beta-catenin signaling appeared to be the most directly involved. In conclusion, both AZA and SAM showed a relevant antitumor activity on NED-CRPC cell lines. This opens a new scenario in the therapy of this lethal variant of prostate cancer.
Project description:DNA methylation is an epigenetic modification that specifies the basic state of pluripotent stem cells and regulates the developmental transition from stem cells to various cell types. In flowering plants, the shoot apical meristem (SAM) contains a pluripotent stem cell population which generates the aerial part of plants including the germ cells. Under appropriate conditions, the SAM undergoes a developmental transition from a leaf-forming vegetative SAM to an inflorescence- and flower-forming reproductive SAM. While SAM characteristics are largely altered in this transition, the complete picture of DNA methylation remains elusive. Here, by analyzing whole-genome DNA methylation of isolated rice SAMs in the vegetative and reproductive stages, we found that methylation at CHH sites is kept high, particularly at transposable elements (TEs), in the vegetative SAM relative to the differentiated leaf, and increases in the reproductive SAM via the RNA-dependent DNA methylation pathway. We also found that half of the TEs that were highly methylated in gametes had already undergone CHH hypermethylation in the SAM. Our results indicate that changes in DNA methylation begin in the SAM long before germ cell differentiation to protect the genome from harmful TEs.
Project description:DNA methylation alterations are a universal feature of cancer. In prostate cancer, site specific DNA methylation changes have been suggested as driver in disease initial and progression. Here we provide a comprehensive assessment of DNA methylation changes in prostate cancer patient derived xenograft (PDX) models. We delineate patterns of both site specific and global methylation changes and nominate novel candidates for biomarker development. Genome wide DNA methylation profiling of prostate cancer patient derived xenograft and cell line models using Infinium EPIC arrays
Project description:DNA methylation alterations are a universal feature of cancer. In prostate cancer, site specific DNA methylation changes have been suggested as driver in disease initial and progression. Here we provide a comprehensive assessment of DNA methylation changes in prostate cancer patient derived xenograft (PDX) models. We delineate patterns of both site specific and global methylation changes and nominate novel candidates for biomarker development. Genome wide DNA methylation profiling of prostate cancer patient derived xenograft and cell line models using Infinium EPIC arrays
Project description:DNA methylation alterations are a universal feature of cancer. In prostate cancer, site specific DNA methylation changes have been suggested as driver in disease initial and progression. Here we provide a comprehensive assessment of DNA methylation changes in prostate cancer patient derived xenograft (PDX) models. We delineate patterns of both site specific and global methylation changes and nominate novel candidates for biomarker development.
Project description:Progesterone receptor membrane component 1 (PGRMC1) is a protein that has been implicated in cancer biology and poor patient outcomes, which can be over-expressed in cancers, and exist in alternative states of phosphorylation.Here, we show that manipulation of PGRMC1 phosphorylation by mutagenesis results in altered cell metabolism. We examine the pathway by which nicotinamide-N-methyl transferase (NNMT) transfers a methyl group from S-adenosylmethionine (SAM) to produce 1-methylnicotinamide, lowering the levels of global methyl donor SAM. Hypothesizing that PGRMC1 phosphorylation status affects genome methylation, we discovered that each of several mutants elicited distinct patterns of CpG methylation.We conclude that PGRMC1 phosphorylation status, as controlled by unknown signaling processes, causes profound changes in cellular plasticity by affecting mechanisms also associated with early embryological tissue differentiation.