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MiRNA-451 is a potential biomarker for estrogenicity in mouse uterus

Lingyan HOU, Yun LU, Ying LI, Li LI

《环境科学与工程前沿（英文）》 2014年第8卷第1期页码 99-105 doi: 10.1007/s11783-013-0490-7

摘要： The uterotrophic assay has been commonly used to test environmental estrogens in vivo, however, it is often not sensitive enough sometimes. An alternative way is to evaluate estrogenicity through biomarker genes. MicroRNA (miRNA) is a class of regulatory gene, which has been shown to be a good biomarker for many diseases and toxicological effects in recent years, and some evidences showed that estrogen induced response was partially mediated by miRNAs. In this study, two types of microarrays were used to test the 17β-estradiol (E2) induced miRNA expression profile at different time points in the immature mouse uterus. Statistical analysis showed the aldehyde slide based array had less variation than the amino slide based array, and 11 dysregulated miRNAs were screened out for significant fold change. Real-time PCR was performed to further confirm that 4 out of 7 selected miRNAs, namely miR-451, miR-155, miR-335-5p, and miR-365, are E2 regulated miRNAs in the uterus. The function of the predicted targets of these miRNAs is involved in cell grow control, which is consistent with the main E2 function in the uterus. MiR-451 had similar strong responses to E2 in the uterus of both immature and overiectomized mice, and could be a potential biomarker for estrogenicity in the uterus.

关键词： estrogen microRNA (miRNA) microarray biomarker

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

Rui Duan, Yun Lu, Lingyan Hou, Lina Du, Lequn Sun, Xingfan Tang

《环境科学与工程前沿（英文）》 2016年第10卷第6期 doi: 10.1007/s11783-016-0880-8

摘要： Estrogen regulates miRNA expression in a typical U-shaped dose-response pattern. E2 can regulate 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 ), and whose expression returned to the control level at a larger dose (200 mg·kg ). 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.

关键词： miRNA Prostate Estradiol Nonmonotonic dose-response Estrogenicity Drosha