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The function of uterine UDP-glucuronosyltransferase 1A8 (UGT1A8) and UDP-glucuronosyltransferase 2B7 (UGT2B7) is involved in endometrial cancer based on estrogen metabolism regulation

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Abstract

Background

The progression of endometrial cancer (EC) is closely related to estrogen levels. UDP-glucuronosyltransferases (UGTs) are an essential class of phase II metabolizing enzymes that play a pivotal role in detoxifying steroid hormone.

Purpose

In this study, we aimed to uncover the role of UGTs in estrogen metabolism and the pathogenesis of EC.

Methods

A total of 100 unrelated EC patients (mean age 52.15 ± 10.04 y) and 100 healthy subjects (mean age 50.26 ± 8.80 y) were recruited for analysis of the UGT gene polymorphism and estrogen level. In six cases of EC, EC-adjacent tissues and cancer tissues were collected for detection of UGT expression.

Results

Our results showed that the estrogen homeostasis profile was disturbed in EC patients, with carcinogenic catechol estrogens (4-OHE1, 2-OHE1, 2-OHE2) significantly accumulated in the serum of these patients. Also, levels of estrogen-glucuronides were decreased significantly, and the expression of UGT1A8 and UGT2B7 in uterine tissues was downregulated in EC patients. Consistent with this, we observed that the distribution of genotypes and allele frequencies in UGT1A8 rs1042597 and UGT2B7 rs7439366 was significantly different between EC patients and healthy volunteers.

Conclusion

These results indicated that UGT1A8 and UGT2B7 may contribute to the estrogen signaling pathway and the pathogenesis of EC.

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Funding

This study was supported by the Graduate Student Research Innovation Projects in Jiangsu Province (KYCX18_2199); the Natural Science Foundation of the Jiangsu Higher Education Institutions of China (No. 18KJA350002); the Natural Science Foundation of Jiangsu Province (No. BK20181470, No. BK20161179); the Science and Technology Foundation of Xuzhou (No. KC18044); the Natural Science Foundation of China (No. 81403001); the special financial grant from the China Postdoctoral Science Foundation (No. 2016T90510); the China Postdoctoral Science Foundation funded the project (No. 2015 M580474); the Six Talent Peaks Project in Jiangsu Province (YY-045); the Qing Lan Project in Jiangsu Province and a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

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Author notes

  1. Feng Zhao and Xi Wang contributed equally to this work.

Authors and Affiliations

  1. Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, 221004, China

    Feng Zhao, Xi Wang & Xueyan Zhou

  2. Department of Obstetrics and Gynecology, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical University, Xuzhou, China

    Jingbo Zhang & Bei Zhang

  3. Department of Pharmacy, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China

    Yan Wang & Ran Lai

Authors
  1. Feng Zhao
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  2. Xi Wang
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  3. Yan Wang
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  4. Jingbo Zhang
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  5. Ran Lai
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  6. Bei Zhang
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Contributions

XYZ and FZ contributed to the conception and design. FZ, XYZ, and XW performed the methodology. FZ, YW, and RL collected experimental data. FZ and XW analyzed and explained the data. FZ and XYZ wrote, reviewed, and revised the manuscript. XYZ, YW, BZ, and JBZ contributed to the administrative, technical, and material support. XYZ supervised the research. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Xueyan Zhou.

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The authors declare that they have no competing interests.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. This study is registered on the Clinical Test Public Management Platform (Registration number: ChiCTR1800014658).

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Informed consent was obtained from all individual participants included in the study.

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Zhao, F., Wang, X., Wang, Y. et al. The function of uterine UDP-glucuronosyltransferase 1A8 (UGT1A8) and UDP-glucuronosyltransferase 2B7 (UGT2B7) is involved in endometrial cancer based on estrogen metabolism regulation. Hormones 19, 403–412 (2020). https://doi.org/10.1007/s42000-020-00213-x

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