Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: D. Mitchell, Robert, Wallace, Andrew D., Hodgson, Ernest, Roe, R. Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5666786/
https://www.ncbi.nlm.nih.gov/pubmed/28991164
http://dx.doi.org/10.3390/ijms18102104
_version_ 1783275372476891136
author D. Mitchell, Robert
Wallace, Andrew D.
Hodgson, Ernest
Roe, R. Michael
author_facet D. Mitchell, Robert
Wallace, Andrew D.
Hodgson, Ernest
Roe, R. Michael
author_sort D. Mitchell, Robert
collection PubMed
description 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.
format Online
Article
Text
id pubmed-5666786
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-56667862017-11-09 Differential Expression Profile of lncRNAs from Primary Human Hepatocytes Following DEET and Fipronil Exposure D. Mitchell, Robert Wallace, Andrew D. Hodgson, Ernest Roe, R. Michael Int J Mol Sci Article 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. MDPI 2017-10-07 /pmc/articles/PMC5666786/ /pubmed/28991164 http://dx.doi.org/10.3390/ijms18102104 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
D. Mitchell, Robert
Wallace, Andrew D.
Hodgson, Ernest
Roe, R. Michael
Differential Expression Profile of lncRNAs from Primary Human Hepatocytes Following DEET and Fipronil Exposure
title Differential Expression Profile of lncRNAs from Primary Human Hepatocytes Following DEET and Fipronil Exposure
title_full Differential Expression Profile of lncRNAs from Primary Human Hepatocytes Following DEET and Fipronil Exposure
title_fullStr Differential Expression Profile of lncRNAs from Primary Human Hepatocytes Following DEET and Fipronil Exposure
title_full_unstemmed Differential Expression Profile of lncRNAs from Primary Human Hepatocytes Following DEET and Fipronil Exposure
title_short Differential Expression Profile of lncRNAs from Primary Human Hepatocytes Following DEET and Fipronil Exposure
title_sort differential expression profile of lncrnas from primary human hepatocytes following deet and fipronil exposure
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5666786/
https://www.ncbi.nlm.nih.gov/pubmed/28991164
http://dx.doi.org/10.3390/ijms18102104
work_keys_str_mv AT dmitchellrobert differentialexpressionprofileoflncrnasfromprimaryhumanhepatocytesfollowingdeetandfipronilexposure
AT wallaceandrewd differentialexpressionprofileoflncrnasfromprimaryhumanhepatocytesfollowingdeetandfipronilexposure
AT hodgsonernest differentialexpressionprofileoflncrnasfromprimaryhumanhepatocytesfollowingdeetandfipronilexposure
AT roermichael differentialexpressionprofileoflncrnasfromprimaryhumanhepatocytesfollowingdeetandfipronilexposure