Effects of Trichloroethylene on the Expression of Long Intergenic Noncoding RNAs in B6C3F1 Mouse Liver

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.

Knockdown of lncRNA LINC01234 Suppresses the Tumorigenesis of Liver Cancer via Sponging miR-513a-5p

“…Intracellular lncRNAs are known to suppress the biological activity of miRNAs and regulate the expression of mRNAs targeted by miRNAs through competing endogenous RNAs (ceRNAs) ( 11 ). Therefore, lncRNAs have been considered to be important targets for treating multiple diseases ( 12 , 13 ). Moreover, lncRNAs play key roles in malignant tumors, including liver cancer ( 14 , 15 ).…”

Macrophage autophagy contributes to immune liver injury in trichloroethylene sensitized mice: Critical role of TNF‐α mediating mTOR pathway

“…Occupational medicamentosa‐like Dermatitis induced by Trichloroethylene (OMDT) may occur in some occupational workers exposed to TCE (Li et al, 2019). In recent years, many studies have found that OMDT patients not only present with severe systemic skin damage, but are also accompanied by multiple organ damage such as heart, liver, and kidney, liver injury is one of the main causes of death (Iritas et al, 2021; Ren et al, 2020). However, the pathogenesis of liver injury is unclear, which seriously restricts the treatment and prevention of OMDT.…”

“…liver, and kidney, liver injury is one of the main causes of death (Iritas et al, 2021;Ren et al, 2020). However, the pathogenesis of liver injury is unclear, which seriously restricts the treatment and prevention of OMDT.…”

Knockdown of lncRNA LINC01234 suppresses the tumorigenesis of liver cancer via sponging miR-513a-5p

“…Previous reports have indicated the importance of lncRNAs in modulating cancer-related signaling pathways (12,13). Moreover, lncRNAs may be related with types of malignant tumors and serve as key factors for tumorigenesis of many cancers (14).…”