Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

RNA-seq of human BR.1N and HaCaT cell lines treated with zebularine against untreated controls

ABSTRACT: 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.

INSTRUMENT(S): Illumina HiSeq 2500

ORGANISM(S): Homo sapiens

SUBMITTER: Alina Mieczkowska

PROVIDER: E-MTAB-6832 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Publications

Epigenetic inhibitor zebularine activates ear pinna wound closure in the mouse.

Sass Piotr P Sosnowski Paweł P Podolak-Popinigis Justyna J Górnikiewicz Bartosz B Kamińska Jolanta J Deptuła Milena M Nowicka Ewa E Wardowska Anna A Ruczyński Jarosław J Rekowski Piotr P Rogujski Piotr P Filipowicz Natalia N Mieczkowska Alina A Peszyńska-Sularz Grażyna G Janus Łukasz Ł Skowron Piotr P Czupryn Artur A Mucha Piotr P Piotrowski Arkadiusz A Rodziewicz-Motowidło Sylwia S Pikuła Michał M Sachadyn Paweł P

EBioMedicine 20190711

<h4>Background</h4>Most studies on regenerative medicine focus on cell-based therapies and transplantations. Small-molecule therapeutics, though proved effective in different medical conditions, have not been extensively investigated in regenerative research. It is known that healing potential decreases with development and developmental changes are driven by epigenetic mechanisms, which suggests epigenetic repression of regenerative capacity.<h4>Methods</h4>We applied zebularine, a nucleoside i ...[more]

PMID: 31303499

Similar Datasets

Revealing the transitory and local effect of the demethylation agent zebularine on plant development and proteome dynamics of Salix purpurea

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

Effect of zebularine on primary human liver cancer cell lines

Project description:Transcriptomic changes in human liver cancer cell lines caused by the demethylating drug zebularine. Epigenomic changes such as aberrant hypermethylation and subsequent atypical gene silencing are characteristic features of human cancer. Here, we report a comprehensive characterization of epigenomic modulation caused by zebularine, an effective DNA methylation inhibitor, in human liver cancer. Using transcriptomic and epigenomic profiling, we identified a zebularine signature that classified liver cancer cell lines into two major subtypes with different drug-responses. In drug-sensitive cell lines, zebularine caused inhibition of proliferation coupled with increased apoptosis, whereas drug-resistant cell lines were associated with upregulation of oncogenic networks (e.g. E2F1, MYC, and TNF) driving liver cancer growth in vitro and in mice. Assessment of zebularine-based therapy in xenograft mouse models demonstrated potent therapeutic effects against tumors established from zebularine-sensitive but not zebularine-resistant liver cancer cells leading to increased survival and decreased pulmonary metastasis. Integration of zebularine gene expression and demethylation response signatures differentiated patients with HCC according to their survival and disease recurrence and identified a subclass of patients within the poor survivors likely to benefit from therapeutic agents that target the cancer epigenome. Each cell line was mock treated or treated with 100uM and 200uM zebularine for 7 days, respectively *** This Series represents the gene expression component of the study.

2011-07-30 | E-GEOD-23991 | biostudies-arrayexpress

DNMT inhibition in the Neonatal Preoptic Area

Project description:PN2 male and female rat pups were treated with vehicle or zebularine. POA RNA was extracted and sequenced to deterime the effects of DNMT inhibition in POA gene expression. Males and Females were treated with either vehicle (0.1% DNMSO in saline) or Zebularine

2015-03-30 | E-GEOD-66203 | biostudies-arrayexpress

DNA methyltransferase inhibitor zebularine inhibits human hepatic carcinoma cells proliferation and induces apoptosis.

Project description:Hepatocellular carcinoma is one of the most common cancers in world wide. During tumorigenesis, tumor suppressor and cancer-related genes are commonly silenced by aberrant DNA methylation in their promoter regions. Zebularine [1-(β-ᴅ-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 hepatocellular carcinoma cell line HepG2. Here, we demonstrated that zebularine exhibited antitumor activity on HepG2 cells by inhibiting cell proliferation and inducing apoptosis. Zebularine treatment down-regulated CDK2 and phosphorylation of retinoblastoma protein (RB), and up-regulated p21WAF/CIP1 and p53. We also found that zebularine treatment up-regulated phosphorylation of p44/42 MAPK. These results suggest that p44/42 MAPK pathway play a role in zebularine induced cell cycle arrest by regulating activity of p21WAF/CIP1 and Rb. Furthermore, we found that zebularine induced apoptosis. Although proapoptotic protein Bax levels were not affected, antiapoptotic protein Bcl-2 level was down-regulated with zebularine treatment. The data in the present study suggest that the action of the double-stranded RNA-dependent protein kinase (PKR) is involved in inducing apoptosis with zebularine. These results provide a novel mechanism of zebularine-induced cell growth arrest and apoptosis in hepatocellular carcinoma. Three each independent batches of zebuluarine-treated and control HepG2 cells were subjected to illumina Human methylation 450K Beadchip analysis.

2013-12-01 | E-GEOD-42490 | biostudies-arrayexpress

Epigenetic Based Enrichment of Cancer Stem Cells: Mechanistic and Clinical Implications for Liver Cancer

Project description:Global transcriptiome changes between SP and NSP cells of liver cancer cell lines w and w/o Zebularine treatment Huh7,WRL68, KMCH FACS sorted in SP and NSP w and w/o Zebularine and subjected to illumina microarray analysis.

2011-10-03 | E-GEOD-24520 | biostudies-arrayexpress

Treatment of prostate cancer cell lines DU-145 and LNCaP with zebularine

Project description:Cultures of DU-145 cells and of LNCaP cells were treated for 216 hours with 100ÂµM 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 (100ÂµM zebularine) DU-145 cells (experiment HK_21_DU_145-HK_26_DU_145), and of untreated and treated (100ÂµM 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

Treatment of renal cell carcinoma cell line A-498 with zebularine

Project description:Cultures of A-498 cells were treated for 120hours with 1000ÂµM 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 (1000ÂµM 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

Zebularine effect on mouse embryonic stem cells manifested as cardiod-myogenic potential: testable hypothesis generation using microarray data

Project description:Lineage commitment during Embryonic Stem Cells (ESCs) differentiation is controlled not only by a gamut of transcription factors but also by epigenetic events, mainly histone deacetylation and promoter DNA methylation. Moreover, the DNA demethylation agent 5′-Aza-2′-deoxycytidine (AzadC) has been widely described in the literature as an effective chemical stimulus used to promote cardiomyogenic differentiation in various stem cell types; however, its toxicity and instability complicate its use. Thus, the purpose of this study was to examine the effects of zebularine, a stable and non-toxic DNA cytosine methylation inhibitor, on ESCs differentiation. Herein are the Affymetrix Expression data obtained from RNA of murine ESCs treated with zebularine. 9 control samples (replicates) and 9 zebularine samples (replicates).

2011-05-05 | E-GEOD-29072 | biostudies-arrayexpress

Global microRNA expression analysis in HaCaT human keratinocytes at low and high cell densities

Project description:Global downregulation of microRNAs (miRNAs) is commonly observed in human cancers and can have a causative role in tumorigenesis. The mechanisms responsible for this phenomenon remain poorly understood. Here we show that YAP, the downstream target of the tumor-suppressive Hippo signaling pathway regulates miRNA biogenesis in a cell density-dependent manner. At low cell density, nuclear YAP binds and sequesters p72 (DDX17), a regulatory component of the miRNA processing machinery. At high cell density, Hippo-mediated cytoplasmic retention of YAP facilitates p72 association with Microprocessor and binding to a specific sequence motif in pri-miRNAs. Inactivation of the Hippo pathway or expression of constitutively active YAP causes widespread miRNA suppression in cells and tumors and a corresponding post-transcriptional induction of MYC expression. Thus, the Hippo pathway links contact-inhibition regulation to miRNA biogenesis and may be responsible for the widespread miRNA repression observed in cancer. Two conditions (Low density and High density) were analyzed in duplicate.

2014-03-03 | E-GEOD-52187 | biostudies-arrayexpress

RNA-Seq of human regulatory T cells and effector T cells cultured at standard 37C temperature and in mild hypothermia (33C).

Project description:Regulatory T cells (Tregs) play crucial role in maintenance of peripheral tolerance. Numerous clinical trials confirmed safety and efficacy of Treg treatment of for deleterious immune responses. However, Tregs lose their characteristic phenotype and suppressive potential during expansion ex vivo. In our experiment we demonstrate that mild hypothermia of 33C induces robust proliferation of human Tregs, preserves expression of FoxP3, CD25 and Helios, and prevents TSDR methylation during culture in vitro. Tregs expanded at 33C showed stronger immunosuppressive potential and anti-inflammatory phenotype. We show that a simple change in temperature can preserve Treg stability, function and accelerate their proliferation in vitro.

2017-10-04 | E-MTAB-5322 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data