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Series GSE80018 Query DataSets for GSE80018
Status Public on Apr 08, 2016
Title Time series trancriptional profiling of mouse liver after up to 13 weeks administration of Phenobarbital [mRNA]
Organism Mus musculus
Experiment type Expression profiling by array
Summary The molecular events during nongenotoxic carcinogenesis and their temporal order are poorly understood but thought to include long-lasting perturbations of gene expression. Here, we have investigated the temporal sequence of molecular and pathological perturbations at early stages of phenobarbital (PB) mediated liver tumor promotion in vivo. Molecular profiling (mRNA, microRNA [miRNA], DNA methylation, and proteins) of mouse liver during 13 weeks of PB treatment revealed progressive increases in hepatic expression of long noncoding RNAs and miRNAs originating from the Dlk1-Dio3 imprinted gene cluster, a locus that has recently been associated with stem cell pluripotency in mice and various neoplasms in humans. PB induction of the Dlk1-Dio3 cluster noncoding RNA (ncRNA) Meg3 was localized to glutamine synthetase-positive hypertrophic perivenous hepatocytes, sug- gesting a role for β-catenin signaling in the dysregulation of Dlk1-Dio3 ncRNAs. The carcinogenic relevance of Dlk1-Dio3 locus ncRNA induction was further supported by in vivo genetic dependence on constitutive androstane receptor and β-catenin pathways. Our data identify Dlk1-Dio3 ncRNAs as novel candidate early biomarkers for mouse liver tumor promotion and provide new opportunities for assessing the carcinogenic potential of novel compounds.
 
Overall design To male B6C3F1/Crl mice were administered Phenobarbital (PB, 0.05% [wt/vol] in drinking water) was administered through ad libitum access to drinking water. The control group received drinking water ad libitum without PB. Mice were sacrificed after 1, 3, 7, 14, 28, 57, and 91 days of PB adminstration, and liver was removed, split into several sections, either frozen in liquid nitrogen and stored at −80°C for subsequent analyses.
 
Contributor(s) Römer M, Harri L
Citation(s) 23091169
Submission date Apr 07, 2016
Last update date Feb 11, 2019
Contact name Jonathan Moggs
E-mail jonathan.moggs@novartis.com
Organization name Novartis
Street address Fabrikstrasse 2
City Basel
ZIP/Postal code 4056
Country Switzerland
 
Platforms (1)
GPL1261 [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
Samples (69)
GSM2111120 H2O_1d_1
GSM2111121 H2O_1d_2
GSM2111122 H2O_1d_3
This SubSeries is part of SuperSeries:
GSE68387 IMI MARCAR Project: towards novel biomarkers for cancer risk assessment
Relations
BioProject PRJNA317638

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE80018_RAW.tar 253.2 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table

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