Fishing for microRNAs in Toxicology

Freeman, Jennifer L.; Weber, Gregory J.; Sepúlveda, Marı́a S.

doi:10.1002/9781118695999.ch4

Cited by 6 publications

(7 citation statements)

References 159 publications

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“…Here we show a novel finding that short term exposure to BPA changed the expression of 15 miRNAs in the liver of adult male zebrafish. Zebrafish provide many advantages as toxicology models and miRNAs are currently most extensively studied and identified in the zebrafish compared to other fish models [ 134 ]. However, only a few studies have examined the effect of BPA exposure on the zebrafish epigenome [ 70 , 135 , 136 , 137 ], and among these, none have specifically considered miRNAs.…”

Section: Discussionmentioning

confidence: 99%

“…However, only a few studies have examined the effect of BPA exposure on the zebrafish epigenome [ 70 , 135 , 136 , 137 ], and among these, none have specifically considered miRNAs. Approximately 392 dre-miRNAs have been identified and entered in miRBase.org database [ 100 ] and several articles have studied some aspect of miRNA function in zebrafish such as their role in basic development and in disease pathways [see Table 4.2 in Freeman et al’s review [ 134 ]]. However this field of research is in its infancy and the function of several dre-miRNAs remain to be defined.…”

Section: Discussionmentioning

confidence: 99%

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The Plasticizer Bisphenol A Perturbs the Hepatic Epigenome: A Systems Level Analysis of the miRNome

Renaud

Silveira

Hazard

et al. 2017

Genes

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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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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The Plasticizer Bisphenol A Perturbs the Hepatic Epigenome: A Systems Level Analysis of the miRNome

Renaud

Silveira

Hazard

et al. 2017

Genes

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“…Additionally, rare minnows have been widely applied in aquatic toxicity testing as a model vertebrate species for many years in our laboratory [ 27 , 28 , 30 – 34 ]. In the field of toxicology studies, several fish models are currently in use; however, research aimed at investigating miRNA alterations is mainly conducted in vitro, and in vivo studies remain in infancy [ 35 ]. The discovery of miRNA genes in the rare minnow genome will contribute to a better understanding of the roles played by miRNAs in regulating diverse biological processes in fish.…”

Section: Introductionmentioning

confidence: 99%

Identification and characterization of novel and conserved microRNAs in several tissues of the Chinese rare minnow (Gobiocypris rarus) based on illumina deep sequencing technology

et al. 2016

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Background: MicroRNAs (miRNAs), which comprise a large family of endogenous small non-coding RNA molecules, play important roles in the regulation of gene expression in various biological processes. The Chinese rare minnow (Gobiocypris rarus) is a Chinese native fish species and is used extensively as an experimental fish in China; however, relevant biological data, especially miRNA transcriptome data, have not been well documented. To discover conserved and potential novel miRNAs in Chinese rare minnows, a pool of equal amounts of RNA obtained from 6 different adult rare minnow tissues (brain, eye, gill, liver, muscle and heart) was sequenced using illumina deep sequencing technology. Results: In the present study, 26,930,553 raw reads, representing 2,118,439 unique high-quality reads, were obtained from the pooled small RNA library. Using bioinformatics analysis, 352 conserved and 112 novel Chinese rare minnow miRNAs were first discovered and characterized in this study. Moreover, we found extensive sequence variations (isomiRs) in rare minnow miRNAs, including internal miRNA isomiRs and terminal isomiRs at both the 5′ and 3′ ends and nucleotide variants. Six conserved and 4 novel miRNAs were selected and validated in 6 different adult rare minnow tissues using quantitative real-time PCR (qPCR). The results showed that miR-30a, miR-30b, and Novel-37 are ubiquitously expressed in a variety of tissues. miR-16a, miR-9, miR-125b, miR-34a, and Novel-69 were predominantly expressed in the brain. Novel-115 and Novel-7 were highly expressed in gills, but were relatively weakly expressed in other tissues. These results provided the expression patterns of miRNA genes in Chinese rare minnow. Finally, based on bioinformatics predictions, we mainly found that Novel-94 and Novel-1b-5p were simultaneously targeted to the 3′UTR of Dmrt1, which controls sex determination and/or sexual differentiation in a variety of metazoans at different sites. Novel-29b targeted the 3′UTR of Foxl2, which is involved in the maintenance of ovarian function and the transcriptional regulation of gonadal differentiation-related genes. Novel-62 and Novel-53 targeted the 3′UTR of ERbeta1 and ERbeta2 (which regulate the transcription of target genes), respectively.

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“…Coupled together, they bind to the target mRNA sequence that is complementary to the mature miRNA sequence and induce mRNA degradation or block protein translation. studies have focused on identifying alterations in DNA methylation associated with environmental chemical exposure, few studies have evaluated deregulation of microRNAs (miRNAs) (Freeman, Weber, & Sepúlveda, 2014). miRNAs are a class of small noncoding RNA that are approximately 22 nucleotides in length and are involved in a number of developmental processes.…”

Section: An Epigenetic Look At Atrazine Toxicitymentioning

confidence: 99%

An Epigenetic Look at Atrazine Toxicity: An Analysis of MicroRNA-126 Expression in Developing Zebrafish Exposed to the Herbicide Atrazine

Schlotman¹

2014

JPUR

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Atrazine is a commonly used herbicide in the United States that is reported to contaminate drinking water sources. Studies indicate atrazine adversely impacts the neuroendocrine and reproductive systems, and that it may be a potential carcinogen. The current maximum contaminant level in drinking water is 3 parts per billion (ppb); however, levels higher than 3 ppb are often reported. Ongoing studies in our laboratory are investigating the immediate and latent adverse health outcomes associated with a developmental atrazine exposure and identifying the genetic and epigenetic mechanisms of toxicity using the zebrafish model system. MicroRNAs (miRNAs) are epigenetic regulators that posttranscriptionally control the translation of mRNA. A preliminary study indicated expression of miR-126, a miRNA associated with angiogenesis and tumorigenesis, to be altered following an embryonic atrazine exposure. To further investigate the developmental expression of miR-126 in zebrafish, quantitative PCR (qPCR) was used to profile expression throughout embryogenesis. Expression of miR-126 was developmental time point specific with significant peaks in expression at 36, 60, and 72 hours postfertilization (hpf). The deregulation of miR-126 by atrazine was also tested using qPCR. Zebrafish embryos exposed to 0.3, 3, or 30 ppb of atrazine were compared to a control treatment at all six developmental time points. While a dose-response trend in upregulation at 36 hpf and in down-regulation at 48 hpf was observed, a significant increase in expression was only observed at 60 hpf in embryos exposed to 30 ppb atrazine. This study is providing a greater understanding of an epigenetic mechanism of atrazine toxicity. Schlotman, K. E. (2013

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Fishing for microRNAs in Toxicology

Cited by 6 publications

References 159 publications

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

Identification and characterization of novel and conserved microRNAs in several tissues of the Chinese rare minnow (Gobiocypris rarus) based on illumina deep sequencing technology

An Epigenetic Look at Atrazine Toxicity: An Analysis of MicroRNA-126 Expression in Developing Zebrafish Exposed to the Herbicide Atrazine

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