Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA258282 | ENA |
REPOSITORIES: ENA
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Project description:Cholangiocarcinoma (CCA) is a cancer arising from the neoplastic transformation of cholangiocytes. During tumorigenesis, tumor suppressor and cancer-related genes are commonly silenced by aberrant DNA methylation in their promoter regions. Zebularine (1-(β-D-ribofuranosyl)-1,2-dihydropyrimidin-2-one) acts as an inhibitor of DNA methylation and exhibits chemical stability and minimal cytotoxicity both in vitro and in vivo. In this study, we explore the effect and possible mechanism of action of zebularine on CCA cells. We demonstrate that zebularine exerts an antitumor effect on CCA cells. Zebularine treatment decreased the concentrations of DNA methyltransferase (DNMT) proteins, and DNMT1 knockdown led to apoptotic cell death in the CCA cell lines TFK-1 and HuCCT1. DNA methylation analysis demonstrated that zebularine induced DNA demethylation, and the GO Biological Process terms “hemophilic cell adhesion”, “regulation of transcription, DNAdependent” and “Wnt signaling pathway” were found to be significantly enriched in association with demethylated genes. Furthermore, we observed that zebularine treatment decreased β-catenin protein levels in TFK-1 and HuCCT1 cells. These results suggest that zebularine alters DNA methylation status, and that some aspect of DNA demethylation by zebularine induces suppression of the Wnt signaling pathway, which leads to apoptotic cell death in CCA. We previously reported a novel mechanism of zebularine-induced cell growth arrest and apoptosis in hepatocellular carcinoma via a DNA methylation-independent pathway. Together, our present and previous studies indicate that zebularine could function as both a DNMT inhibitor and a non-DNMT inhibitor reagent, and that, while the optimal usage of zebularine may depend on cancer type, zebularine may be useful for chemotherapy against cancer.
2015-03-24 | GSE60446 | GEO
Project description:The experimental design demonstrates that zebularine, a DNA methyltransferase inhibitor, promotes regeneration in the mouse and that retinoic acid and zebularine synergistically accelerate this process.
2019-11-02 | E-MTAB-6832 | biostudies-arrayexpress
Project description:DNA methyltransferase inhibitor zebularine inhibits human hepatic carcinoma cells proliferation and induces apoptosis.
| PRJNA182141 | ENA
Project description:Cultures of DU-145 cells and of LNCaP cells were treated for 216 hours with 100µM zebularine (SIGMA) in three independent biological experiments. Zebularine acts as a DNA methyltransferase (DNMT) inhibitor thereby upregulating genes that are inactivated by e.g. promotor hypermethylation. The experiment aimed to search for upregulated transcripts to provide new targets for biomarker development and therapeutic use. Total RNA of untreated and treated (100µM zebularine) DU-145 cells (experiment HK_21_DU_145-HK_26_DU_145), and of untreated and treated (100µM zebularine) LNCaP cells (experiment HK_27_LNCaP-HK_32_LNCaP), were subjected to Affymetrix array analysis to detail the overall expression changes after treatment with a DNMT inhibitor. Treated cells showed no obvious signs of zebularine-induced cytotoxicity as revealed by XTT assays.
2013-10-24 | E-GEOD-51629 | biostudies-arrayexpress
Project description:Cultures of DU-145 cells and of LNCaP cells were treated for 216 hours with 100µM zebularine (SIGMA) in three independent biological experiments. Zebularine acts as a DNA methyltransferase (DNMT) inhibitor thereby upregulating genes that are inactivated by e.g. promotor hypermethylation. The experiment aimed to search for upregulated transcripts to provide new targets for biomarker development and therapeutic use.
2013-10-24 | GSE51629 | GEO
Project description:Cultures of A-498 cells were treated for 120hours with 1000µM zebularine (SIGMA) in three independent biological experiments. Zebularine acts as a DNA methyltransferase (DNMT) inhibitor thereby upregulating genes that are inactivated by e.g. promotor hypermethylation. The experiment aimed to search for upregulated transcripts to provide new targets for biomarker development and therapeutic use. 308 candidates were upregulated more than 1.5-fold. Members of the metallothionein group (MT1G, MT1H, and MT2A) were validated in 49 clinical samples of renal cell carcinomas. Total RNA of treated (1000µM zebularine) and untreated A-498 cells (experiment A05-A07) was subjected to Affymetrix array analysis to detail the overall expression changes after treatment with a DNMT inhibitor. Treated cells showed no obvious signs of zebularine-induced cytotoxicity as revealed by XTT assays. Cell were split twice during the 120hour treatment period.
2013-10-24 | E-GEOD-51627 | biostudies-arrayexpress
Project description:Cultures of A-498 cells were treated for 120hours with 1000µM zebularine (SIGMA) in three independent biological experiments. Zebularine acts as a DNA methyltransferase (DNMT) inhibitor thereby upregulating genes that are inactivated by e.g. promotor hypermethylation. The experiment aimed to search for upregulated transcripts to provide new targets for biomarker development and therapeutic use. 308 candidates were upregulated more than 1.5-fold. Members of the metallothionein group (MT1G, MT1H, and MT2A) were validated in 49 clinical samples of renal cell carcinomas.
2013-10-24 | GSE51627 | GEO
Project description:Zebularine is a non-methylable cytidine analog that is used in epigenetic and cancer research. Its application has been shown to activate several transcriptionally silenced genetic elements; however, extent of this activation and other effects on the transcriptome are unknown. Here, we show that zebularine treatment induces preferentially genes associated with DNA damage repair response and this activation is strongly ATR-dependent. The set of up- and down-regulated genes after 24 h zebularine treatment is almost fully contained in the set of genes with changed transcription in response to 24 h MMC treatment. We identified only few genes that were up-regulated in common by longer (5 days) zebularine treatment and loss of epigenetic control in ddm1 mutant. Our results suggest that zebularine does not induce global activation of targets of transcriptional gene silencing and indicate previously unanticipated DNA damaging effects associated with zebularine-treatment.
2014-11-18 | GSE63355 | GEO
Project description:DNA methylation plays major roles in the epigenetic regulation of gene expression, transposon and transcriptional silencing, and DNA repair, with implications in developmental processes and phenotypic plasticity. Relevantly for arboreal species, DNA methylation constitute a regulative layer in cell wall dynamics associated with xylogenesis. The use of methyltransferase and/or demethylase inhibitors has been proven informative to shed light on the methylome dynamics behind the regulation of these processes. The present work employs the cytidine analog zebularine to inhibit DNA methyltransferases and induce DNA hypomethylation in Salix purpurea plantlets grown in vitro and in soil. An integrative approach has been adopted to highlight the effects of hypomethylation on proteomic dynamics, exposing the age-specific (three weeks of in vitro culture and one month of growth in soil) and tissue-specific (shoot and root) effects following exposure to zebularine. Significant proteomic shifts were revealed in the development from in vitro to in-soil culture and, whereas zebularine treatment decreased methylation in three-weeks roots, a functionally heterogeneous subset of protein entries was differentially accumulated in shoot samples, including entries associated with cell wall dynamics, tissue morphogenesis, and hormonal regulation. The identification of tissue-specific proteomic hallmarks in combination with hypomethylating agents provides new insights into the role of DNA methylation in early plant development in willow species.
2024-01-08 | PXD045653 | Pride
Project description:Zebularine is a non-methylable cytidine analog that is used in epigenetic and cancer research. Its application has been shown to activate several transcriptionally silenced genetic elements; however, extent of this activation and other effects on the transcriptome are unknown. Here, we show that zebularine treatment induces preferentially genes associated with DNA damage repair response and this activation is strongly ATR-dependent. The set of up- and down-regulated genes after 24 h zebularine treatment is almost fully contained in the set of genes with changed transcription in response to 24 h MMC treatment. We identified only few genes that were up-regulated in common by longer (5 days) zebularine treatment and loss of epigenetic control in ddm1 mutant. Our results suggest that zebularine does not induce global activation of targets of transcriptional gene silencing and indicate previously unanticipated DNA damaging effects associated with zebularine-treatment. Examination of transcriptional changes in response to mock, 24 h and 5 days 20 uM zebularine and 24 h 10 uM MMC treatment in Arabidopsis wild-type and/or atr-2.
2014-11-18 | E-GEOD-63355 | biostudies-arrayexpress