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Gene expression profiles of liver tissues (normal, non-tumor and tumor tisuues) of F2 males of C3H mice born to F1 mice gestationally exposed to arsenite

ABSTRACT: Gene expression profiles of liver tissues (normal, non-tumor and tumor tisuues) of F2 males of C3H mice born to F1 mice gestationally exposed to arsenite

PROVIDER: PRJNA509674 | ENA |

REPOSITORIES: ENA

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The DNA methylation profiles of liver tissues (normal, non-tumor and tumor tisuues) of F2 males of C3H mice born to F1 mice gestationally exposed to arsenite

Project description:Background: Previously, we showed that gestational arsenite (As) exposure of F0 females increases hepatic tumors in the F2 males in C3H mice. However, the mechanisms have not yet been clarified. Methods: We detected genome wide site-specific DNA methylation by using reduced representative bisulfite sequence (RRBS) method. We used the data uploaded here and those with GSE Series accession number GSE111420 (CCN and CCTt) to detect differential methyrated cytosines between control groups and arsenite groups. Results: We clarified that DNA methylation of Tmem54 and Cd74 around TSS were downregulated and their gene expressions were accordingly upregulated in the liver tumor tissues of F2 males of arsenite group. Conclusions: Our study proposes novel DNA methylation dependent pathways which increase liver tumors in the F2 males of arsenite group.

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Gene expression profiles of liver tissues (normal, non-tumor and tumor tisuues) of F2 males of C3H mice born to F1 mice gestationally exposed to arsenite

Project description:We have employed microarray analysis to detect gene expression changes that were affected in the F2 mice of arsenite group.

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Project description:Multigenerational adverse effects from the environment such as nutrition and chemicals are among important concerns in environmental health issues. Previously, we have found that arsenite exposure of only F0 females during their pregnancy increases hepatic tumors in the F2 males in C3H mice. In the current study, we investigated the association of DNA methylation with the hepatic tumor increase in the F2 males of the arsenite group. Reduced-representation bisulfite sequencing analysis newly identified that DNA methylation levels of regions around the transcriptional start sites of Tmem54 and Cd74 were decreased and the expression of these genes were significantly increased in the hepatic tumors of F2 males of the arsenite group. The associations between DNA methylation in these regions and gene expression changes were confirmed by treatment of murine hepatoma cell lines and hepatic stellate cell line with 5-aza-2'-deoxycytidine. Overexpression of Cd74 in Hepa1c1c7 cells increased Trib3 expression and suppressed the expression of tumor suppressor genes Id3 and Atoh8. Human database analysis using the Cancer Genome Atlas indicated that TMEM54, CD74, and TRIB3 were significantly increased and that ATOH8 was decreased in hepatocellular carcinoma. The data also showed that high expression of TMEM54 and TRIB3 and low expression of ATOH8 were associated with poor survival. These results suggested that an increase in Tmem54 and Cd74 expression via DNA methylation reduction was involved in the tumor increase in the F2 male offspring by gestational arsenite exposure of F0 females. This study also suggested that genes downstream of Cd74 were involved in tumorigenesis.

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