miR-130b-5p Regulates Expression of ERβ via IGFBP2/SREBP1 Axis in Human Endometriotic Stromal Cells

Endometriosis is an estrogen-dependent disease. Estrogen receptor β (ERβ), which is highly expressed in endometriotic tissues, is regarded as a key gene contributing to the pathogenesis of endometriosis. Molecular targeted therapy of MicroRNA is emerging as a promising therapeutic regimen. Thus, it is of great significance to explore the targeted MicroRNA to regulate the ERβ expression in endometriosis. Here, we found that miR-130b-5p expression in endometriotic stromal cells (ESCs) was lower than those in eutopic endometrial stromal cells (EMs). In ESCs, miR-130b-5p mimic decreased ERβ expression, while miR-130b-5p inhibitor increased ERβ expression. However, the molecular mechanism of miR-130b-5p regulating the expression of ERβ is unavailable. Markedly increased expression of insulin-like growth factor binding protein 2 (IGFBP2) was observed in ESCs. Transfection with siIGFBP2 resulted in a decrease in ERβ expression in ESCs. In addition, correspondingly decreased or increased expression of IGFBP2 was observed after transfection of miR-130b-5p mimic or inhibitor, and knockdown of IGFBP2 inhibited the miR-130b-5p inhibitor-enhanced ERβ expression in ESCs. Here, we found the binding affinities of sterol regulatory element-binding protein 1 (SREBP1) to the ERβ promoter were higher in ESCs than in EMs. IGFBP2 knockdown significantly decreased the binding activities of SREBP1 to the ERβ promoter. In vivo, miR-130b-5p agomir injection of endometriosis mice resulted in suppression of endometriosis lesions and down-regulation of ERβ expression. Our results demonstrate a critical role of miR-130b-5p in the pathogenesis of endometriosis, suggesting a potential druggable target for future therapy. Similar content being viewed by others Data Availability The datasets used during the present study are available from the corresponding author upon reasonable request.

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Author information Authors and Affiliations Contributions Peili Wu performed the experiments and statistical analysis. Jingwen Zhu contributed to clinical sample collection and experimental guidance. Qing Xue critically revised the manuscript. All authors contributed to the article and approved the submitted version. Corresponding author Ethics declarations Ethics Approval and Consent to Participate The research protocol involving human specimen was given the green light by the Institutional Review Board of Peking University of First Hospital (No.2021[445]). Ethics approval for experimental studies involving animals were given by the Laboratory Animal Ethics Committee of Peking University of First Hospital (No.J2023103). Competing interests The authors declare that they have no competing interests. Additional information Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Rights and permissions Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. About this article Cite this article Wu, P., Zhu, J. & Xue, Q. miR-130b-5p Regulates Expression of ERβ via IGFBP2/SREBP1 Axis in Human Endometriotic Stromal Cells. Reprod. Sci. 33, 372–382 (2026). https://doi.org/10.1007/s43032-025-02036-w Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s43032-025-02036-w