Department of Obstetrics and Gynecology, Peking University First Hospital, No.1 Xi'anmen Street, Beijing, 100034, China.
Department of Reproductive Medicine, Key Laboratory for Major Obstetric Diseases of Guangdong Province, and Key Laboratory for Reproduction and Genetics of Guangdong Higher Education Institutes, the Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Reprod Sci. 2023 Jul;30(7):2188-2197. doi: 10.1007/s43032-021-00734-9. Epub 2023 Jan 17.
Endometriosis (EMS) is an estrogen-dependent disease. However, little is known about the regulation of estrogen, a potential therapeutic target, in EMS, which remains very poorly managed in the clinic. We hypothesized that microRNAs (miRNAs) can be exploited therapeutically to regulate transcription factor 21 (TCF21) and steroidogenic factor-1 (SF-1) gene expression. In our study, paired eutopic and ectopic endometrial samples were obtained from women with EMS and processed by a standard protocol to obtain human endometrial stromal cells (EMs) for in vitro studies. We found that miR-92a-3p levels were decreased in ectopic endometrium and ectopic stromal cells (ESCs) compared with paired eutopic lesions. miR-92a-3p overexpression significantly suppressed the proliferation and migration of ESCs, whereas a decreased level of miR-92a-3p generated the opposite results. Next, we identified TCF21 as a candidate target gene of miR-92a-3p. In vitro cell experiments showed that miR-92a-3p negatively regulated the expression of TCF21 and its downstream target gene SF-1. Moreover, cell proliferation and invasion ability decreased after the silencing of SF-1 and increased after SF-1 overexpression. We also observed that silencing SF-1 while inhibiting miR-92a-3p partially blocked the increase in cell proliferation and invasion ability caused by miR-92a-3p knockdown while overexpressing both SF-1 and miR-92a-3p mitigated the impairment in cell proliferation and invasion ability caused by miR-92a-3p overexpression. Our results may provide a novel potential therapeutic target for the treatment of EMS.
子宫内膜异位症 (EMS) 是一种雌激素依赖性疾病。然而，人们对雌激素的调控知之甚少，而雌激素是一个潜在的治疗靶点，在临床上仍难以有效治疗。我们假设 microRNAs (miRNAs) 可用于治疗，以调控转录因子 21 (TCF21) 和类固醇生成因子-1 (SF-1) 基因的表达。在我们的研究中，从患有 EMS 的女性中获得配对的在位和异位子宫内膜样本，并通过标准方案处理，以获得用于体外研究的人子宫内膜基质细胞 (EMs)。我们发现，与配对的在位病变相比，异位子宫内膜和异位基质细胞 (ESCs) 中的 miR-92a-3p 水平降低。miR-92a-3p 的过表达显著抑制 ESCs 的增殖和迁移，而 miR-92a-3p 水平的降低则产生相反的结果。接下来，我们确定 TCF21 是 miR-92a-3p 的候选靶基因。体外细胞实验表明，miR-92a-3p 负调控 TCF21 及其下游靶基因 SF-1 的表达。此外，SF-1 沉默后细胞增殖和侵袭能力降低，SF-1 过表达后则增加。我们还观察到，SF-1 沉默同时抑制 miR-92a-3p 部分阻断了 miR-92a-3p 敲低引起的细胞增殖和侵袭能力的增加，而同时过表达 SF-1 和 miR-92a-3p 则减轻了 miR-92a-3p 过表达引起的细胞增殖和侵袭能力的损害。我们的研究结果可能为治疗 EMS 提供了一个新的潜在治疗靶点。
