Department of Reproductive Medicine, Affiliated Hospital of Shandong Second Medical University, Weifang, Shandong Province, 261041, P.R. China.
Department of Emergency, Affiliated Hospital of Shandong Second Medical University, Weifang, Shandong Province, 261041, P.R. China.
Endocrinology. 2024 Feb 20;165(4). doi: 10.1210/endocr/bqae018.
Ovarian endometriosis (EMs) is a benign, estrogen-dependent gynecological disorder. Estrogen receptor beta (ERβ), a nuclear receptor for estradiol, plays an important role in the development of ovarian EMs. Here, we investigated the biological significance of aurora kinase A (AURKA) in ovarian EMs and the mechanism by which it regulates ERβ. We used immunohistochemical assays to verify that AURKA and ERβ were highly expressed in ectopic endometrial tissues. Cell proliferation and colony formation assays were used to demonstrate that AURKA promoted the proliferation of EMs cells. Wound-healing assay, Transwell migration assay, and Matrigel invasion assay further showed that AURKA enhanced the ability of EMs cells to migrate and invade. In addition, AURKA was shown to stimulate glycolysis in EMs cells by measuring the concentration of glucose and lactate in the cell supernatants. Moreover, the AURKA inhibitor alisertib was found to inhibit the progression of ovarian EMs and glycolysis in a mouse model of EMs by measuring ectopic tissues as well as by testing the peritoneal fluid of mice. Furthermore, coimmunoprecipitation assay showed that AURKA interacted with ERβ. The rescue experiments confirmed that AURKA regulated the development and glycolysis of ovarian EMs in an ERβ-dependent manner. AURKA contributed to the development of ovarian EMs by upregulating of ERβ. AURKA may represent a new target for the treatment of ovarian EMs.
卵巢子宫内膜异位症（EMs）是一种良性、雌激素依赖性妇科疾病。雌激素受体β（ERβ）是雌激素的核受体，在卵巢 EMs 的发生发展中起重要作用。在这里，我们研究了极光激酶 A（AURKA）在卵巢 EMs 中的生物学意义及其调节 ERβ的机制。我们使用免疫组织化学检测证实 AURKA 和 ERβ在异位子宫内膜组织中高表达。细胞增殖和集落形成实验表明 AURKA 促进了 EMs 细胞的增殖。划痕愈合实验、Transwell 迁移实验和 Matrigel 侵袭实验进一步表明 AURKA 增强了 EMs 细胞的迁移和侵袭能力。通过测量细胞上清液中葡萄糖和乳酸的浓度，还表明 AURKA 刺激了 EMs 细胞的糖酵解。此外，通过测量异位组织和小鼠的腹腔液，发现 AURKA 抑制剂alisertib 通过抑制卵巢 EMs 和 EMs 小鼠模型中的糖酵解来抑制卵巢 EMs 的进展。进一步的免疫共沉淀实验表明 AURKA 与 ERβ相互作用。通过转染 ERβ siRNA 的挽救实验证实 AURKA 通过 ERβ 依赖性方式调节卵巢 EMs 的发生和糖酵解。AURKA 通过上调 ERβ 促进卵巢 EMs 的发生发展。AURKA 可能成为治疗卵巢 EMs 的新靶点。
