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Int. J. Mol. Sci. 2017, 18(10), 2104; doi:10.3390/ijms18102104

Differential Expression Profile of lncRNAs from Primary Human Hepatocytes Following DEET and Fipronil Exposure

1
Department of Entomology and Plant Pathology, North Carolina Agromedicine Institute, Campus Box 7647, 3230 Ligon Street, North Carolina State University, Raleigh, NC 27695, USA
2
Toxicology Program, Department of Biology, North Carolina State University, Raleigh, NC 27695, USA
3
Department of Applied Ecology, Toxicology Program, Department of Biology, North Carolina Agromedicine Institute, North Carolina State University, Raleigh, NC 27695, USA
*
Author to whom correspondence should be addressed.
Received: 15 August 2017 / Revised: 4 October 2017 / Accepted: 4 October 2017 / Published: 7 October 2017
(This article belongs to the Section Molecular Toxicology)
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Abstract

While the synthesis and use of new chemical compounds is at an all-time high, the study of their potential impact on human health is quickly falling behind, and new methods are needed to assess their impact. We chose to examine the effects of two common environmental chemicals, the insect repellent N,N-diethyl-m-toluamide (DEET) and the insecticide fluocyanobenpyrazole (fipronil), on transcript levels of long non-protein coding RNAs (lncRNAs) in primary human hepatocytes using a global RNA-Seq approach. While lncRNAs are believed to play a critical role in numerous important biological processes, many still remain uncharacterized, and their functions and modes of action remain largely unclear, especially in relation to environmental chemicals. RNA-Seq showed that 100 µM DEET significantly increased transcript levels for 2 lncRNAs and lowered transcript levels for 18 lncRNAs, while fipronil at 10 µM increased transcript levels for 76 lncRNAs and decreased levels for 193 lncRNAs. A mixture of 100 µM DEET and 10 µM fipronil increased transcript levels for 75 lncRNAs and lowered transcript levels for 258 lncRNAs. This indicates a more-than-additive effect on lncRNA transcript expression when the two chemicals were presented in combination versus each chemical alone. Differentially expressed lncRNA genes were mapped to chromosomes, analyzed by proximity to neighboring protein-coding genes, and functionally characterized via gene ontology and molecular mapping algorithms. While further testing is required to assess the organismal impact of changes in transcript levels, this initial analysis links several of the dysregulated lncRNAs to processes and pathways critical to proper cellular function, such as the innate and adaptive immune response and the p53 signaling pathway. View Full-Text
Keywords: DEET; fipronil; long non-coding RNA; lncRNA; primary liver cells; epigenetics; RNA-Seq; transcriptomics; Zika virus; human hepatocytes DEET; fipronil; long non-coding RNA; lncRNA; primary liver cells; epigenetics; RNA-Seq; transcriptomics; Zika virus; human hepatocytes
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Mitchell III, R.D.; Wallace, A.D.; Hodgson, E.; Roe, R.M. Differential Expression Profile of lncRNAs from Primary Human Hepatocytes Following DEET and Fipronil Exposure. Int. J. Mol. Sci. 2017, 18, 2104.

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