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Environ Toxicol. 2015 May-Jun;30(6):712-23. doi: 10.1002/tox.21949. Epub 2014 Jan 13.

Prenatal and neonatal exposure to perfluorooctane sulfonic acid results in aberrant changes in miRNA expression profile and levels in developing rat livers.

Author information

1
School of Environmental Science and Technology, Dalian University of Technology, Key Laboratory of Industrial Ecology and Environmental Engineering, MOE, Dalian, 116024, China.
2
Department of Biological Science, Luoyang Normal University, Luoyang, 471022, China.

Abstract

Perfluorooctane sulfonate (PFOS) is an animal carcinogen. However, the underlying mechanism in cancer initiation is still largely unknown. Recently identified microRNAs (miRNAs) may play an important role in toxicant exposure and in the process of toxicant-induced tumorigenesis. We used PFOS to investigate PFOS-induced changes in miRNA expression in developing rat liver and the potential mechanism of PFOS-induced toxic action. Dams received 3.2 mg/kg PFOS in their feed from gestational day 1 (GD1) to postnatal day 7 (PND 7). Pups then had free access to treated feed until PND 7. We isolated RNAs from liver tissues on PND 1 and 7 and analyzed the expression profiles of 387 known rat miRNAs using microarray technology. PFOS exposure induced significant changes in miRNA expression profiles. Forty-six miRNAs had significant expression alterations on PND 1, nine miRNAs on PND 7. Specifically, expression of four miRNAs was up-regulated on PND 7 but down-regulated on PND1 (p < 0.05). Many aberrantly expressed miRNAs were related to various cancers. We found oncogenic and tumor-suppressing miRNAs, which included miR-19b, miR-21*, miR-17-3p, miR-125a-3p, miR-16, miR-26a, miR-1, miR-200c, and miR-451. In addition, four miRNAs were simultaneous significantly expressed on both PND 1 and 7. Functional Annotation analysis of the predicted transcript targets revealed that PFOS exposure potentially alters pathways associated with different cancers (cancer, melanoma, pancreatic cancer, colorectal cancer, and glioma), biological processes which include positive regulation of apoptosis and cell proliferation. Results showed PFOS exposure altered the expression of a suite of miRNAs.

KEYWORDS:

PFOS; carcinogenesis; developmental toxicity; microRNA; microarray

PMID:
24420840
DOI:
10.1002/tox.21949
[Indexed for MEDLINE]

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