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

doi:10.1007/s11783-016-0880-8

Front. Environ. Sci. Eng.

2016, Vol. 10

Issue (6) : 11 https://doi.org/10.1007/s11783-016-0880-8

RESEARCH ARTICLE

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

State Key Joint Laboratory of Environment Simulation and Pollution Control, School of Environment, Tsinghua University, Beijing 100084, China

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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.

Keywords miRNA Prostate Estradiol Nonmonotonic dose-response Estrogenicity Drosha

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Corresponding Author(s): Yun Lu

Issue Date: 19 October 2016

Cite this article:

Rui Duan,Yun Lu,Lingyan Hou, et al. U-shaped microRNA expression pattern could be a new concept biomarker for environmental estrogen[J]. Front. Environ. Sci. Eng., 2016, 10(6): 11.

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https://academic.hep.com.cn/fese/EN/10.1007/s11783-016-0880-8
https://academic.hep.com.cn/fese/EN/Y2016/V10/I6/11

Fig.1 Changes in bodyweight (BW) after E₂ treatment. The weight gain was calculated by subtracting the pretreatment BW from the BW on the final day. Values are means±SD. No significant difference was found (n = 10) by ANOVA Tukey test

Fig.2 Effect of E₂ treatment on the morphology of epithelial cells in the ventral prostate. (a) An H&E-stained section from a control ventral lobe. The black frame encloses the region enlarged in (b). (b) Enlarged image showing epithelial cells with two different shapes. ‘a’ represents a typical columnar cell shape; and ‘b’ is a cuboidal cell shape. A schematic drawing is shown next to each image. (c) Columnar and cuboidal epithelial cell length ratios. CK denotes control groupValues are means±SD. A ‘*’ denotes a significant difference from the control group by ANOVA Tukey test at p<0.05

Fig.3 microRNAs regulated by E₂ in the ventral lobe. ((a)and(b)) The effects of treatment with 0 (control), 0.2, 2, 20, and 200 mg·kg^-¹ E₂ on microRNA expression levels. CK denotes control group. The control was assigned a value of 1.0. Values are means±SD. A ‘*’ denotes a significant difference from the control group by ANOVA Tukey test at p<0.05

Fig.4 microRNAs regulated by E₂ in the anterior lobe. The effects of treatment with 0 (control), 0.2, 2, 20, and 200 mg·kg^-¹ E₂ on microRNA expression levels. CK denotes control group. The control was assigned a value of 1.0. Values are means±SD. A ‘*’ denotes a significant difference from the control group by ANOVA Tukey test at p<0.05

Fig.5 MicroRNAs regulated by E₂ in the dorsolateral lobe. The effects of treatment with 0 (control), 0.2, 2, 20, and 200 mg·kg^-¹ E₂ on microRNA expression levels. CK denotes control group. The control was assigned a value of 1.0. Values are means±SD. A ‘*’ denotes a significant difference from the control group by ANOVA Tukey test at p<0.05

Fig.6 miRNAs regulated by E₂ in all three prostate lobes. vp, ventral prostate; ap, anterior prostate; and dlp, dorsolateral prostate. The numbers of miRNAs whose expression was significantly influenced by E₂ treatment are shown under the names of the prostate lobes

Fig.7 Regulation of Drosha and Dicer expression by E₂ in the ventral lobe. E₂ doses of 0 (control), 0.2, 2, 20, and 200 mg·g^-¹ were used. The control was assigned a value of 1.0. Values are means±SD. A ‘*’ denotes a significant change from the control by ANOVA Tukey test at p<0.05

Tab.1 Top 10 pathways involving the target genes of E₂-regulated miRNAs

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