The Plasticizer Bisphenol A Perturbs the Hepatic Epigenome: A Systems Level Analysis of the miRNome.
The Plasticizer Bisphenol A Perturbs the Hepatic Epigenome: A Systems Level Analysis of the miRNome.
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DOI：
10.3390/genes8100269
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发表时间：
2017-10-13
期刊：
影响因子：
3.5
通讯作者：
Hardiman G
中科院分区：
文献类型：
--
作者：
Renaud L;Silveira WAD;Hazard ES;Simpson J;Falcinelli S;Chung D;Carnevali O;Hardiman G
双酚A（BPA）是一种内分泌干扰物（艾德），它的广泛暴露已经引起了人们对人类和生态系统健康的关注。表观遗传因子，包括microRNAs（miRNAs），是癌症期间基因表达的关键调节因子。BPA暴露对斑马鱼表观基因组的影响仍然很差。斑马鱼是研究癌症的绝佳模型，因为该生物体会产生类似于人类癌症的疾病。使用斑马鱼作为系统毒理学模型，我们假设慢性BPA暴露会影响成年斑马鱼的miRNome，并建立一个更容易发生癌症的表观基因组。暴露于100 nM BPA 3周后，提取肝脏RNA进行高通量mRNA和miRNA测序。使用已建立的生物信息学管道进行差异表达（DE）分析，比较BPA暴露于对照标本。在BPA暴露的肝脏中，6188个mRNA和15个miRNA表达不同（q ≤ 0.1）。通过分析DE斑马鱼基因的人类直系同源物，发现了与非酒精性脂肪肝（NAFLD），氧化磷酸化，线粒体功能障碍和细胞周期相关的特征。长期暴露于BPA对成年斑马鱼的肝脏miRNome和转录组有显著影响，可能导致包括癌症在内的不良健康后果。
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.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
10.5
作者：
Chen, PY;Manninga, H;Tuschl, T
通讯作者：
Tuschl, T
影响因子：
30.8
作者：
Bentwich, I;Avniel, A;Bentwich, Z
通讯作者：
Bentwich, Z
影响因子：
14.9
作者：
Chen J;Bardes EE;Aronow BJ;Jegga AG
通讯作者：
Jegga AG
影响因子：
30.8
作者：
Chen, JF;Mandel, EM;Wang, DZ
通讯作者：
Wang, DZ