U-shaped microRNA expression pattern could be a new concept biomarker for environmental estrogen

Abstract

Estrogen regulates miRNA expression in a typical U-shaped dose-response pattern.

E2 can regulate drosha in the ventral prostate.

Mouse ventral prostate is most sensitive to estrogen.

Nonmonotonic dose-response in prostate could be a component of estrogen signature.

Many studies have focused on environmental estrogen-related diseases. However, no consistent gene markers or signatures for estrogenicity have been discovered in mammals. This study investigated the estrogenic effects of 17β-estradiol on the prostate in immature male mice. Consistent U-shaped responses were seen in bodyweight, ventral prostate epithelial morphology, and miRNA expression levels. Specifically, most estradiol regulated miRNAs were downregulated at low doses of estradiol (0.2 and 2 mg·kg⁻¹), and whose expression returned to the control level at a larger dose (200 mg·kg⁻¹). The function of these regulated miRNAs is related to the prostate cancer and PI3K-Akt signaling pathways, which is consistent with the function of estradiol. Furthermore, the miRNA-processing machinery, Drosha, in the prostate was also regulated in a similar pattern, which could be a part of the U-shaped miRNA expression mechanism. All of these data indicate that the prostate is a reliable organ for evaluating estrogenic activity and that the typical nonmonotonic dose-response relationship could be used as a novel biomarker for estrogenicity.

Graphical abstract

Keywords

miRNA / Prostate / Estradiol / Nonmonotonic dose-response / Estrogenicity / Drosha

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