Female-to-male differential transcription patterns of miRNA-mRNA networks in the livers of dioxin-exposed mice.

Abstract

Non-coding microRNAs (miRNAs) have important roles in regulating the expression of liver mRNAs in response to xenobiotic-exposure, but their roles concerning dioxins such as TCDD (2,3,7,8-Tetrachlorodibenzo-p-dioxin) are less clear. This report concerns the potential implication of liver (class I) and circulating (class II) miRNAs in hepatotoxicity of female and male mice after acute exposure to TCDD. The data show that, of a total of 38 types of miRNAs, the expression of eight miRNAs were upregulated in both female and male mice exposed to TCDD. Inversely, the expression of nine miRNAs were significantly downregulated in both animal genders. Moreover, certain miRNAs were preferentially induced in either females or males. The potential downstream regulatory effects of miRNAs on their target genes was evaluated by determining the expression of three group of genes that are potentially involved in cancer biogenesis, other diseases and in hepatotoxicity. It was found that certain cancer-related genes were more highly expressed females rather than males after exposure to TCDD. Furthermore, a paradoxical female-to-male transcriptional pattern was found for several disease-related and hepatotoxicity-related genes. These results suggest the possibility of developing of new miRNA-specific interfering molecules to address their dysfunctions as caused by TCDD.