Endometriosis (EMs) is an estrogen (E2)-dependent inflammatory disorder. Although EMs is considered a benign disease, it presents with malignant characteristics, such as migration and invasion. An increasing number of studies have shown that aberrantly expressed circular RNAs (circRNAs) play an essential role in disease development and progression. However, the mechanisms by which circRNAs exert their pathological effects in EMs remain unclear. Hsa_circ_0001649, a novel cancer-associated circRNA, has been previously reported to be downregulated in several cancer types and related to cell migration and invasion. In the present study, real-time PCR (qRT-PCR) was carried out to measure hsa_circ_0001649 levels in human tissues, human primary endometrial stromal cells (ESCs) and a human endometrial stromal cell line (ThESCs). Matrix metalloproteinase 9 (MMP9) levels in ESCs and ThESCs were assessed by qRT-PCR and Western blotting, and the migration and invasion capacities of ThESCs were evaluated by transwell assay. As a result, hsa_circ_0001649 expression was significantly decreased in ectopic and eutopic endometrial samples compared with that in normal endometrial samples. E2 decreased hsa_circ_0001649 expression but increased MMP9 expression in ESCs and ThESCs. Furthermore, ThESCs were more invasive under E2 stimulation. However, these effects disappeared when ICI or hsa_circ_0001649 transfection was used. Collectively, our findings reveal that decreased hsa_circ_0001649 expression plays a role in E2-increased MMP9 expression through E2 receptors (ERs), which have critical functions in EMs.

中文翻译：

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雌激素减少的 hsa_circ_0001649 促进子宫内膜异位症的基质细胞侵袭

子宫内膜异位症 (EMs) 是一种雌激素 (E2) 依赖性炎症性疾病。虽然 EMs 被认为是一种良性疾病，但它具有恶性特征，如迁移和侵袭。越来越多的研究表明，异常表达的环状 RNA（circRNA）在疾病的发展和进展中发挥着重要作用。然而，circRNAs在EMs中发挥病理作用的机制尚不清楚。Hsa_circ_0001649 是一种新型的癌症相关 circRNA，先前已报道在几种癌症类型中下调并与细胞迁移和侵袭有关。在本研究中，进行实时 PCR (qRT-PCR) 以测量人体组织、人类原代子宫内膜基质细胞 (ESC) 和人类子宫内膜基质细胞系 (ThESC) 中 hsa_circ_0001649 的水平。通过qRT-PCR和Western印迹评估ESCs和ThESCs中基质金属蛋白酶9（MMP9）水平，并通过Transwell测定评估ThESCs的迁移和侵袭能力。结果，与正常子宫内膜样品相比，异位和在位子宫内膜样品中 hsa_circ_0001649 的表达显着降低。E2 降低了 hsa_circ_0001649 的表达，但增加了 ESC 和 ThESC 中 MMP9 的表达。此外，在 E2 刺激下，ThESCs 更具侵入性。然而，当使用 ICI 或 hsa_circ_0001649 转染时，这些影响消失了。总的来说，我们的研究结果表明，hsa_circ_0001649 表达的降低通过 E2 受体 (ER) 在 E2 增加的 MMP9 表达中起作用，E2 受体在 EM 中具有关键功能。