Genes 2017, 8(10), 269; https://doi.org/10.3390/genes8100269
The Plasticizer Bisphenol A Perturbs the Hepatic Epigenome: A Systems Level Analysis of the miRNome
Ludivine Renaud 1,2, Willian A. da Silveira 3, E. Starr Hazard 3,4, Jonathan Simpson 3, Silvia Falcinelli 5, Dongjun Chung 7, Oliana Carnevali 5
and Gary Hardiman 1,2,3,6,7,*
and Gary Hardiman 1,2,3,6,7,*
1
Division of Nephrology, Department of Medicine, Medical University of South Carolina (MUSC),Charleston, SC 29425, USA
2
Laboratory for Marine Systems Biology, Hollings Marine Laboratory, Charleston, SC 29412, USA
3
Center for Genomic Medicine, Bioinformatics, Medical University of South Carolina (MUSC), Charleston, SC 29425, USA
4
Library Science and Informatics, Medical University of South Carolina (MUSC), Charleston, SC 29425, USA
5
Dipartimento Scienze della Vita e dell’Ambiente, Universita Politecnica delle Marche, 60131 Ancona, Italy
6
Department of Medicine, University of California, La Jolla, CA 92093, USA
7
Department of Public Health Sciences, Medical University of South Carolina (MUSC), Charleston, SC 29425, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Laura Sánchez
Received: 31 July 2017 / Revised: 18 September 2017 / Accepted: 4 October 2017 / Published: 13 October 2017
(This article belongs to the Special Issue Zebrafish: The Key for Cancer Treatment)
Abstract
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. View Full-TextKeywords:
bisphenol A; epigenome; microRNAs; zebrafish; toxicology; bioinformatics
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Renaud, L.; Silveira, W.A.; Hazard, E.S.; Simpson, J.; Falcinelli, S.; Chung, D.; Carnevali, O.; Hardiman, G. The Plasticizer Bisphenol A Perturbs the Hepatic Epigenome: A Systems Level Analysis of the miRNome. Genes 2017, 8, 269.
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