Abstract：
:Trichloroethylene (TCE), a widely used industrial solvent, is a common environmental contaminant. We previously reported that TCE-induced changes in DNA methylation and miRNA expression contributed to the development of a liver tumor in mice. In this study, we investigated the role of long intergenic noncoding RNA (LincRNA), another type of epigenetic modification, in TCE hepatocarcinogenesis. Male B6C3F1 mice were gavaged with TCE at dose levels of 0, 100, 500, and 1000 mg/kg b.w. for 5 days. The expression changes of LincRNAs in liver samples from control and TCE-exposed mice were screened by microarray. When compared to the control group, 21 and 29 LincRNAs were upregulated and downregulated, respectively, in the liver of mice exposed to TCE at 1000 mg/kg b.w. In addition, TCE treatment increased the expression levels of LincRNA-GM8704 but decreased the expression levels of LiverLincs_chr17_4383_2 in a dose-dependent manner. We further found that the mRNAs that are highly correlated with the expression of LiverLincs_chr17_4383_2 are involved in a number of cancer-related signaling pathways including PPARs, cell cycle, and ErbB and p53 signaling pathways. Among the expression-correlated mRNAs, Cdkn1a was found to be a downstream target gene of LiverLincs_chr17_4383_2. To follow up on that, we also found that miR-182-5p might mediate the association between downregulation of LiverLincs_chr17_4383_2 and upregulation of Cdkn1a, leading to increased cell proliferation in TCE exposed liver cells. In conclusion, TCE induced extensive LincRNA expression changes in mouse liver, and the downregulation of LiverLincs_chr17_4383_2 might contribute to TCE hepatocarcinogenesis by interacting with miR-182-5p and Cdkn1a.
journal_name
Chem Res Toxicoljournal_title
Chemical research in toxicologyauthors
Ren F,Wang J,Aniagu S,Li J,Jiang Y,Chen Tdoi
10.1021/acs.chemrestox.9b00382subject
Has Abstractpub_date
2020-06-15 00:00:00pages
1356-1363issue
6eissn
0893-228Xissn
1520-5010journal_volume
33pub_type
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