<p>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.</p>