Endometriosis is an estrogen-dependent disease, and estrogen receptor 2 (ESR2) plays a critical role in the pathogenesis of ovarian endometriosis by promoting cell invasion. Yes-associated protein 1 (YAP1) plays suppressive roles in several types of tumors. However, the relationship between YAP1 and ESR2 is not fully understood. The aim of this study was to investigate the regulatory mechanism of YAP1 in terms of ESR2 and YAP1 regulation of endometriotic stromal cell (ECSC) invasion in ovarian endometriosis. Our results demonstrated that YAP1 mRNA and protein levels in eutopic endometrium (EU) tissues were higher than those in paired ectopic endometrium (EC) tissues. ECSCs transfected with siYAP1 exhibited a significant increase in both ESR2 mRNA levels and protein expression. Simultaneously, YAP1 overexpression in ECSCs yielded the opposite results. Co-IP assays demonstrated YAP1-NuRD complex formation by YAP1, CHD4 and MTA1 in ECSCs. YAP1 bound to two sites, (-539, -533) and (-158, -152), upstream of the ESR2 transcription initiation site. YAP1 binding to the two sites of the ESR2 promoter in ECSCs was significantly lower than that in eutopic endometrial stromal cells (EUSCs) from EU tissues. ECSCs transfected with siYAP1 exhibited increased invasion activity, while ECSCs transfected with siESR2 showed inhibition of invasion. However, transfection with siYAP1 and siESR2 together decreased the number of invading cells compared with transfection with siYAP1 alone. Therefore, we conclude that decreased levels of YAP1 in ovarian endometriomas enhance ESR2 expression via formation of a YAP1-NuRD complex, which further binds to the ESR2 promoters. Furthermore, YAP1 inhibits ECSCs invasion.

中文翻译：

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YAP1通过ESR2抑制卵巢子宫内膜异位间质细胞侵袭

子宫内膜异位症是一种雌激素依赖性疾病，雌激素受体2（ESR2）通过促进细胞侵袭在卵巢子宫内膜异位症的发病机制中起关键作用。Yes 相关蛋白 1 (YAP1) 在多种类型的肿瘤中发挥抑制作用。然而，YAP1 和 ESR2 之间的关系尚不完全清楚。本研究的目的是研究 YAP1 在 ESR2 和 YAP1 对卵巢子宫内膜异位症中子宫内膜异位基质细胞 (ECSC) 侵袭的调控方面的调控机制。我们的结果表明，在位子宫内膜 (EU) 组织中的 YAP1 mRNA 和蛋白质水平高于成对的异位子宫内膜 (EC) 组织。用 siYAP1 转染的 ECSCs 表现出 ESR2 mRNA 水平和蛋白质表达的显着增加。同时地，ECSCs 中的 YAP1 过表达产生了相反的结果。Co-IP 分析表明 YAP1、CHD4 和 MTA1 在 ECSC 中形成 YAP1-NuRD 复合物。YAP1 与 ESR2 转录起始位点上游的两个位点 (-539, -533) 和 (-158, -152) 结合。YAP1 与 ECSCs 中 ESR2 启动子的两个位点的结合显着低于来自 EU 组织的在位子宫内膜基质细胞 (EUSCs)。转染siYAP1的ECSCs表现出增加的侵袭活性，而转染siESR2的ECSCs表现出侵袭抑制。然而，与单独用 siYAP1 转染相比，用 siYAP1 和 siESR2 一起转染减少了入侵细胞的数量。因此，我们得出结论，卵巢子宫内膜异位症中 YAP1 水平的降低通过形成 YAP1-NuRD 复合物来增强 ESR2 表达，进一步与 ESR2 启动子结合。此外，YAP1 抑制 ECSCs 侵袭。