Role of Multiple MicroRNAs in the Sexually Dimorphic Expression of Cyp2b9 in Mouse Liver

• DOI: 10.1124/dmd.113.052217
• Publication Date: 2013-05-24T05:17:03Z
• Authors: Xiaofeng Xie; Lingling Miao; Jun Yao; Chenchen Feng; Chenggang Li; Man Gao; Mingxia Liu; Likun Gong; Yizheng Wang; Xinming Qi; Jin Ren
• Keywords: Sexual dimorphism

Mouse cytochrome P450 2b9 (Cyp2b9) is a testosterone 16<i>α</i>-hydroxylase enzyme showing female-specific expression in many inbred mouse strains, including C57BL/6J. Previous studies have recognized that some sex-dependently secreted endogenous modulating factors were involved the sexually dimorphic of Cyp2b9 through transcriptional regulation. In this study, we found evidence microRNAs contributed to biased via post-transcriptional was upregulated livers hepatocyte-specific Dicer1 knockout mice at 3 weeks. The age-dependent downregulation male diminished when specifically knocked out hepatocytes. When these data combined with bioinformatics analysis and microRNA profiles female mice, 18 associated Cyp2b9, which showed higher levels C57BL/6J compared females. Luciferase assays revealed approximate half repressed luciferase activity reporter system containing 3′-untranslated region (3′-UTR) also inhibited protein expression. MicroRNA seed mutation or mutations putative binding sites 3′-UTR led loss suppression activity. There negative correlation between Cyp2b9. Our results suggested multiple participated regulation expression, lower potentially mice.