The Plasticizer Bisphenol A Perturbs the Hepatic Epigenome: A Systems Level Analysis of the miRNome
Autor: | E. Starr Hazard, Jonathan Simpson, Ludivine Renaud, Gary Hardiman, Oliana Carnevali, Silvia Falcinelli, Willian A. da Silveira, Dongjun Chung |
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Jazyk: | angličtina |
Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
endocrine system lcsh:QH426-470 bisphenol A epigenome Bioinformatics Article Transcriptome 03 medical and health sciences 0302 clinical medicine SDG 3 - Good Health and Well-being microRNA Genetics medicine Epigenetics Zebrafish Genetics (clinical) microRNAs zebrafish toxicology bioinformatics biology urogenital system Fatty liver Cancer Epigenome medicine.disease biology.organism_classification 3. Good health lcsh:Genetics 030104 developmental biology Endocrine disruptor 030220 oncology & carcinogenesis Cancer research hormones hormone substitutes and hormone antagonists |
Zdroj: | Genes; Volume 8; Issue 10; Pages: 269 Genes, Vol 8, Iss 10, p 269 (2017) Renaud, L, da Silveira, W A, Hazard, E S, Simpson, J, Falcinelli, S, Chung, D, Carnevali, O & Hardiman, G 2017, ' The Plasticizer Bisphenol A Perturbs the Hepatic Epigenome: A Systems Level Analysis of the miRNome ', Genes, vol. 8, no. 10 . https://doi.org/10.3390/genes8100269 Genes |
ISSN: | 2073-4425 |
DOI: | 10.3390/genes8100269 |
Popis: | Ubiquitous exposure to bisphenol A (BPA), an endocrine disruptor (ED), has raised concerns for both human and ecosystem health. Epigenetic factors, including microRNAs (miRNAs), 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 a disease that resembles human cancer. Using zebrafish as a 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 3 week 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, 6188 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 and transcriptome in adult zebrafish with the potential to cause adverse health outcomes including cancer. |
Databáze: | OpenAIRE |
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