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Association between serum concentrations of perfluoroalkyl substances (PFAS) and expression of serum microRNAs in a cohort highly exposed to PFAS from drinking water

Xu, Yiyi LU ; Jurkovic-Mlakar, Simona ; Li, Ying ; Wahlberg, Karin LU ; Scott, Kristin LU ; Pineda, Daniela LU ; Lindh, Christian H LU orcid ; Jakobsson, Kristina LU and Engström, Karin LU (2020) In Environment International 136.
Abstract

BACKGROUND: Perfluoroalkyl substances (PFAS) are widespread synthetic substances with various adverse health effects. Not much is known about the modes of action of PFAS toxicity, but one likely mechanism is alteration of microRNA expression.

OBJECTIVES: To investigate whether PFAS exposure is associated with altered microRNA expression in serum.

METHODS: We selected women from the Ronneby cohort, with high exposure to perfluorooctane sulfonic acid (PFOS) and perfluorohexane sulfonic acid (PFHxS), emanating from drinking water contaminated by firefighting foam, and a control group of women from a neighbouring municipality without drinking water contamination. Serum levels of PFAS were analysed using LC/MS/MS. High coverage... (More)

BACKGROUND: Perfluoroalkyl substances (PFAS) are widespread synthetic substances with various adverse health effects. Not much is known about the modes of action of PFAS toxicity, but one likely mechanism is alteration of microRNA expression.

OBJECTIVES: To investigate whether PFAS exposure is associated with altered microRNA expression in serum.

METHODS: We selected women from the Ronneby cohort, with high exposure to perfluorooctane sulfonic acid (PFOS) and perfluorohexane sulfonic acid (PFHxS), emanating from drinking water contaminated by firefighting foam, and a control group of women from a neighbouring municipality without drinking water contamination. Serum levels of PFAS were analysed using LC/MS/MS. High coverage microRNA expression was analysed by next generation sequencing (NGS) in 53 individuals to screen for microRNAs associated with PFAS exposure. After verification by qPCR, associations between PFAS exposure and expression of 18 selected microRNAs were validated by qPCR in 232 individuals. In silico functional analyses were performed using Ingenuity pathway analysis (IPA).

RESULTS: Three microRNAs were consistently associated with PFAS exposure in the different steps of the study: miR-101-3p, miR-144-3p and miR-19a-3p (all downregulated with increasing exposure). In silico functional analyses suggested that these PFAS-associated microRNAs were annotated to e.g. cardiovascular function and disease, Alzheimer's disease, growth of cancer cell lines and cancer. Seven predicted target genes for the downregulated microRNAs were annotated to PFAS in IPA knowledge database: DNA methyltransferase 3 alpha (DNMT3a), epidermal growth factor receptor (EGFR), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), nuclear receptor subfamily 1, group H, member 3 (NR1H3), peroxisome proliferator-activated receptor alpha (PPARα), prostaglandin-endoperoxide synthase 2 (PTGS2), and tumour growth factor alpha (TGFα).

DISCUSSION: PFAS exposure was associated with downregulation of specific microRNAs. Further, in silico functional analyses suggest potential links between the specific PFAS-associated microRNAs, specific microRNA target genes and possibly also health effects.

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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Environment International
volume
136
article number
105446
publisher
Elsevier
external identifiers
  • pmid:31926437
  • scopus:85077659186
ISSN
1873-6750
DOI
10.1016/j.envint.2019.105446
language
English
LU publication?
yes
additional info
Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.
id
cc372bac-511e-46b0-81c4-038745c7ec87
date added to LUP
2020-01-17 08:20:55
date last changed
2024-04-17 02:05:42
@article{cc372bac-511e-46b0-81c4-038745c7ec87,
  abstract     = {{<p>BACKGROUND: Perfluoroalkyl substances (PFAS) are widespread synthetic substances with various adverse health effects. Not much is known about the modes of action of PFAS toxicity, but one likely mechanism is alteration of microRNA expression.</p><p>OBJECTIVES: To investigate whether PFAS exposure is associated with altered microRNA expression in serum.</p><p>METHODS: We selected women from the Ronneby cohort, with high exposure to perfluorooctane sulfonic acid (PFOS) and perfluorohexane sulfonic acid (PFHxS), emanating from drinking water contaminated by firefighting foam, and a control group of women from a neighbouring municipality without drinking water contamination. Serum levels of PFAS were analysed using LC/MS/MS. High coverage microRNA expression was analysed by next generation sequencing (NGS) in 53 individuals to screen for microRNAs associated with PFAS exposure. After verification by qPCR, associations between PFAS exposure and expression of 18 selected microRNAs were validated by qPCR in 232 individuals. In silico functional analyses were performed using Ingenuity pathway analysis (IPA).</p><p>RESULTS: Three microRNAs were consistently associated with PFAS exposure in the different steps of the study: miR-101-3p, miR-144-3p and miR-19a-3p (all downregulated with increasing exposure). In silico functional analyses suggested that these PFAS-associated microRNAs were annotated to e.g. cardiovascular function and disease, Alzheimer's disease, growth of cancer cell lines and cancer. Seven predicted target genes for the downregulated microRNAs were annotated to PFAS in IPA knowledge database: DNA methyltransferase 3 alpha (DNMT3a), epidermal growth factor receptor (EGFR), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), nuclear receptor subfamily 1, group H, member 3 (NR1H3), peroxisome proliferator-activated receptor alpha (PPARα), prostaglandin-endoperoxide synthase 2 (PTGS2), and tumour growth factor alpha (TGFα).</p><p>DISCUSSION: PFAS exposure was associated with downregulation of specific microRNAs. Further, in silico functional analyses suggest potential links between the specific PFAS-associated microRNAs, specific microRNA target genes and possibly also health effects.</p>}},
  author       = {{Xu, Yiyi and Jurkovic-Mlakar, Simona and Li, Ying and Wahlberg, Karin and Scott, Kristin and Pineda, Daniela and Lindh, Christian H and Jakobsson, Kristina and Engström, Karin}},
  issn         = {{1873-6750}},
  language     = {{eng}},
  publisher    = {{Elsevier}},
  series       = {{Environment International}},
  title        = {{Association between serum concentrations of perfluoroalkyl substances (PFAS) and expression of serum microRNAs in a cohort highly exposed to PFAS from drinking water}},
  url          = {{http://dx.doi.org/10.1016/j.envint.2019.105446}},
  doi          = {{10.1016/j.envint.2019.105446}},
  volume       = {{136}},
  year         = {{2020}},
}