We report the effects of exposure to the endocrine disurptor (2-ethylhexyl) phthalate (DEHP) on transcriptome modification in the livers of in vivo Zebrafish. Our data indicate changes in fatty acid metabolism and insulin resistance, pathways associated with the development of Non-Alcoholic Fatty Liver Disease (NAFLD). Overall design: Examination of transcriptome changes in an in vivo model organism exposed to a common, environmental compound.
Systems Analysis of the Liver Transcriptome in Adult Male Zebrafish Exposed to the Plasticizer (2-Ethylhexyl) Phthalate (DEHP).
No sample metadata fields
View SamplesCompared to other fish models, miRNAs are currently most extensively studied and identified in zebrafish. Approximately 415 dre-miRNAs have been identified and several articles have studied some aspect of miRNA function in zebrafish such as their role in basic development and in disease pathways. However, this field of research is in its infancy and the function of several dre-miRNAs, as well as their tissue-specific expression profile, are yet to be defined. In this study, the liver and gut were dissected (wildtype/untreated fish), total and small RNA were extracted, mRNA and miRNA libraries constructed and subjected to high throughput sequencing (HTS) using standard approaches. We carried out differential expression (DE) analysis and compared liver miRNA expression to gut using established bioinformatics pipelines. Through bioinformatics analysis, known and putative novel miRNAs were identified. Finally, we constructed a “miRNA matrix” that connects both total RNA-Seq and miRNA-Seq. Overall design: Examination of transcriptome in an in vivo model organism in two defined tissues, liver and gut.
Interplay Between MicroRNAs and Targeted Genes in Cellular Homeostasis of Adult Zebrafish (<i>Danio rerio</i>).
Sex, Specimen part, Subject
View SamplesExposure to bisphenol A (BPA), an endocrine disruptor (ED), has raised concerns for both human and ecosystem health. Epigenetic factors, including microRNAs, are key regulators of gene expression during cancer. The effect of BPA exposure on the zebrafish epigenome remains poorly characterized. Zebrafish represents an excellent model to study cancer as the organism develops disease that resembles human cancer. Using zebrafish as systems toxicology model, we hypothesized that chronic BPA-exposure impacts the miRNome in adult zebrafish and establishes an epigenome more susceptible to cancer development. After a 21 day exposure to 100 nM BPA, RNA from the liver was extracted to perform high throughput mRNA and miRNA sequencing. Differential expression (DE) analyses comparing BPA-exposed to control specimens were performed using established bioinformatics pipelines. In the BPA-exposed liver, 6,188 mRNAs and 15 miRNAs were differently expressed (q = 0.1). By analyzing human orthologs of the DE zebrafish genes signatures associated with non-alcoholic fatty liver disease (NAFLD), oxidative phosphorylation, mitochondrial dysfunction and cell cycle were uncovered. Chronic exposure to BPA has a significant impact on the liver miRNome in adult zebrafish and has the potential to cause adverse outcomes including cancer. Overall design: Examination of transcriptome changes in an in vivo model organism exposed to a common, environmental compound.
The Plasticizer Bisphenol A Perturbs the Hepatic Epigenome: A Systems Level Analysis of the miRNome.
No sample metadata fields
View SamplesPromoter hypermethylation and transcriptional silencing is a common epigenetic mechanism of tumour suppressor inactivation in cancer, including malignant brain tumours.
Epigenetic genome-wide analysis identifies BEX1 as a candidate tumour suppressor gene in paediatric intracranial ependymoma.
Specimen part, Treatment
View SamplesMsi2 is a critical regulatior of myeoid leukemia, and these data identify genes that are changed following Msi2 deletion in bcCML and de novo AML stem cells.
Tetraspanin 3 Is Required for the Development and Propagation of Acute Myelogenous Leukemia.
Specimen part
View SamplesmiRNA-Sequencing was performed on human aortic valve interestitial cells (AVICs) exposed to 14% stretch at 1 hz or static conditions for 24h. Overall design: Six static control and six samples exposed to cyclic stretch 14% for 24h
The stretch responsive microRNA miR-148a-3p is a novel repressor of IKBKB, NF-κB signaling, and inflammatory gene expression in human aortic valve cells.
Specimen part, Subject
View SamplesAVICs were exposed to cyclic stretch to examine the role of mechanical stimuli on gene expression
The stretch responsive microRNA miR-148a-3p is a novel repressor of IKBKB, NF-κB signaling, and inflammatory gene expression in human aortic valve cells.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Chromatinized protein kinase C-θ directly regulates inducible genes in epithelial to mesenchymal transition and breast cancer stem cells.
Cell line, Treatment
View SamplesEpithelial to mesenchymal transition (EMT) is activated during cancer invasion and metastasis, enriches for cancer stem cells (CSCs), and contributes to therapeutic resistance and disease recurrence. The epithelial cell line MCF7, can be induced to undergo EMT with the induction of PKC by PMA. 5-10% of the resulting cells have a CSC phenotype. This study looks at the transcriptome of these cells and how it differs from cells with a non-CSC phenotype.
Chromatinized protein kinase C-θ directly regulates inducible genes in epithelial to mesenchymal transition and breast cancer stem cells.
Cell line, Treatment
View SamplesCDK4/6 kinase inhibitors have shown great promise in clinical trials in various cancer types and have recently entered clinical trial for advanced prostate cancer. Although patients are expected to respond well to this class of drugs, development of resistance in some patients is anticipated. To pre-empt this and study how prostate cancer may evade CDK4/6 inhibition, new resistance models were generated from LNCaP and LAPC4 prostate cancer cells cells by prolonged culturing in presence of 0.5uM palbociclib. RNA sequencing data was integrated with phospho-proteomics to unravel the molecular underpinnings of acquired resistance to palbociclib and resultant broad CDK4/6 inhibitor resistance. Overall design: Thirty total sample: three biological replicates of vehicle control and PD treated parental and Palbociclib (PD) resistant cells (PDR) that were generated from LAPC4 and LNCaP cells.
MAPK Reliance via Acquired CDK4/6 Inhibitor Resistance in Cancer.
Specimen part, Subject
View Samples