Department of Obstetrics & Gynecology, Shengjing Hospital of China Medical University, No.36 Sanhao Street, Heping District, Shenyang, 110004, PR China.
Cell Death Dis. 2020 Jul 29;11(7):594. doi: 10.1038/s41419-020-02784-4.
Endometriosis is a common and benign gynecological disorder but exhibits malignant features. However, the underlying pathogenesis and pathophysiology of endometriosis remain unclear. Circular RNAs have been demonstrated to participate in the occurrence and progression of multiple diseases. This study was aimed to explore the roles of circATRNL1 in endometriosis in vitro. Based on the results of reverse transcription-quantitative polymerase chain reaction analysis, we found significant upregulation of circATRNL1 and Yes-associated protein 1 (YAP1), while downregulation of miR-141-3p and miR-200a-3p in ectopic tissues compared to eutopic tissues. The immunohistochemistry and western blot analysis showed differentially expressed epithelial-mesenchymal transition (EMT) markers between EuEM and EcEM tissues. The in vitro assays indicated that overexpression of circATRNL1 could promote the proliferation, migration, and invasion of Ishikawa cells, and induce EMT process, while circATRNL1 silencing showed the opposite effect. The mechanical investigation indicated that circATRNL1 upregulated YAP1 by sponging miR-141-3p and miR-200a-3p. Gain-of-function assays validated the inhibitory function of miR-141-3p and miR-200a-3p in endometriosis. The results of rescue assays confirmed the function of circATRNL1-miR-141-3p/miR-200a-3p-YAP1 axis on Ishikawa cells. Our findings demonstrate that abnormal upregulation of circATRNL1 regulates cell proliferation and motility and promotes EMT process via the miR-141-3p/miR-200a-3p-YAP1 axis in vitro, which could contribute to the progression of endometriosis.
子宫内膜异位症是一种常见的良性妇科疾病，但具有恶性特征。然而，子宫内膜异位症的发病机制和病理生理学仍不清楚。环状 RNA 已被证明参与多种疾病的发生和发展。本研究旨在探讨 circATRNL1 在子宫内膜异位症中的作用。基于逆转录定量聚合酶链反应分析的结果，我们发现外位组织中 circATRNL1 和 Yes 相关蛋白 1 (YAP1) 显著上调，而 miR-141-3p 和 miR-200a-3p 下调。免疫组织化学和 Western blot 分析显示 EuEM 和 EcEM 组织之间上皮-间充质转化 (EMT) 标志物表达存在差异。体外实验表明，circATRNL1 的过表达可促进 Ishikawa 细胞的增殖、迁移和侵袭，并诱导 EMT 过程，而 circATRNL1 沉默则显示出相反的效果。机制研究表明，circATRNL1 通过海绵吸附 miR-141-3p 和 miR-200a-3p 而上调 YAP1。功能获得实验验证了 miR-141-3p 和 miR-200a-3p 在子宫内膜异位症中的抑制作用。挽救实验的结果证实了 circATRNL1-miR-141-3p/miR-200a-3p-YAP1 轴对 Ishikawa 细胞的功能。我们的研究结果表明，circATRNL1 的异常上调通过 miR-141-3p/miR-200a-3p-YAP1 轴调节细胞增殖和运动，并促进 EMT 过程，这可能有助于子宫内膜异位症的进展。
