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论文类型：期刊论文

发表时间：2015-05-01

发表刊物：ENVIRONMENTAL TOXICOLOGY

收录刊物：SCIE、EI、PubMed、Scopus

卷号：30

期号：6

页面范围：712-723

ISSN号：1520-4081

关键字：PFOS; carcinogenesis; developmental toxicity; microarray; microRNA

摘要：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. (c) 2014 Wiley Periodicals, Inc. Environ Toxicol 30: 712-723, 2015.