Estradiol Promotes Endometriosis Progression Via the ERβ/QKI /circSMAD2 Axis.

IF 2.2 4区医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Current pharmaceutical biotechnology Pub Date : 2025-02-20 DOI:10.2174/0113892010331129250216041033

Yuan Peng, Wenqian Xiong, Haitang He, Hengwei Liu, Tian Fu, Xuefeng Long, Xiaoou Li, Xin Dai, Ying Xu, Ling Zhang, Yi Liu

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Abstract

Aims: The present study aimed to examine the roles of circRNA-circSMAD2 and its regulatory mechanisms in endometriosis (EMs).

Background: Evidence has confirmed that circRNAs play multiple roles in regulating the occurrence and development of EMs, but the regulatory mechanisms of circRNAs in EMs remain largely unknown.

Objective: The roles and regulatory mechanisms of circSMAD2 in EMs.

Method: Eutopic and ectopic endometrium of ovarian EMs as well as normal endometrial tissues, were used to extract circRNA, mRNA, and total proteins. The human endometrial stromal cell lines (ThESCs) and endometrial stromal cells (ESCs) were stimulated with different concentrations or times of 17β-estradiol (E2). The mouse model of EMs was established by implanting uterine horns onto the peritoneum wall using a suture.

Result: Compared with normal tissues, the expression of circSMAD2 was significantly decreased in eutopic and ectopic endometrial tissues. Furthermore, the expression of circSMAD2 was downregulated by E2 in a dose- and time-dependent manner in ThESCs and ESCs. Overexpression of circSMAD2 inhibited the invasion and migration of ThESCs, while knockdown of circSMAD2 exerted the opposite effect. The RNA binding protein quaking (QKI), which is involved in circRNA formation, was lower in eutopic and ectopic endometrial tissues compared to normal tissues.

Conclusion: Moreover, E2 suppressed the expression of circSMAD2 by inhibiting the expression of QKI. Additionally, E2 enabled the expression of estrogen receptor beta (ERβ) to inhibit the expression of QKI and circSMAD2 in vitro and in vivo.

Conclusion: The E2/ERβ/QKI/circSMAD2 pathway was involved in cellular migration and invasion in EMs.

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目的：本研究旨在探讨circRNA-circSMAD2在子宫内膜异位症（EMs）中的作用及其调控机制：背景：有证据证实，circRNA在调控子宫内膜异位症的发生和发展中发挥着多种作用，但circRNA在子宫内膜异位症中的调控机制仍不为人知：circSMAD2在EMs中的作用及调控机制：方法：采用卵巢EMs的异位和异位子宫内膜以及正常子宫内膜组织，提取circRNA、mRNA和总蛋白。用不同浓度或时间的 17β-雌二醇（E2）刺激人子宫内膜基质细胞系（ThESCs）和子宫内膜基质细胞（ESCs）。通过缝合将子宫角植入腹膜壁，建立了小鼠EMs模型：结果：与正常组织相比，异位和异位子宫内膜组织中 circSMAD2 的表达明显降低。此外，在 ThESCs 和 ESCs 中，circSMAD2 的表达受 E2 的影响呈剂量和时间依赖性下调。过表达 circSMAD2 可抑制 ThESCs 的侵袭和迁移，而敲除 circSMAD2 则产生相反的效果。与正常组织相比，异位和异位子宫内膜组织中参与circRNA形成的RNA结合蛋白quaking（QKI）含量较低：结论：E2通过抑制QKI的表达来抑制circSMAD2的表达。此外，E2还能使雌激素受体β（ERβ）的表达在体外和体内抑制QKI和circSMAD2的表达：结论：E2/ERβ/QKI/circSMAD2途径参与了EMs的细胞迁移和侵袭。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current pharmaceutical biotechnology 医学-生化与分子生物学

CiteScore

5.60

自引率

3.60%

发文量

203

审稿时长

6 months

期刊介绍： Current Pharmaceutical Biotechnology aims to cover all the latest and outstanding developments in Pharmaceutical Biotechnology. Each issue of the journal includes timely in-depth reviews, original research articles and letters written by leaders in the field, covering a range of current topics in scientific areas of Pharmaceutical Biotechnology. Invited and unsolicited review articles are welcome. The journal encourages contributions describing research at the interface of drug discovery and pharmacological applications, involving in vitro investigations and pre-clinical or clinical studies. Scientific areas within the scope of the journal include pharmaceutical chemistry, biochemistry and genetics, molecular and cellular biology, and polymer and materials sciences as they relate to pharmaceutical science and biotechnology. In addition, the journal also considers comprehensive studies and research advances pertaining food chemistry with pharmaceutical implication. Areas of interest include: DNA/protein engineering and processing Synthetic biotechnology Omics (genomics, proteomics, metabolomics and systems biology) Therapeutic biotechnology (gene therapy, peptide inhibitors, enzymes) Drug delivery and targeting Nanobiotechnology Molecular pharmaceutics and molecular pharmacology Analytical biotechnology (biosensing, advanced technology for detection of bioanalytes) Pharmacokinetics and pharmacodynamics Applied Microbiology Bioinformatics (computational biopharmaceutics and modeling) Environmental biotechnology Regenerative medicine (stem cells, tissue engineering and biomaterials) Translational immunology (cell therapies, antibody engineering, xenotransplantation) Industrial bioprocesses for drug production and development Biosafety Biotech ethics Special Issues devoted to crucial topics, providing the latest comprehensive information on cutting-edge areas of research and technological advances, are welcome. Current Pharmaceutical Biotechnology is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the latest and most important developments.