Department of Obstetrics & Gynecology, Shengjing Hospital of China Medical University , Shenyang, China.
Cell Cycle. 2020 Jul;19(14):1740-1753. doi: 10.1080/15384101.2020.1777804. Epub 2020 Jun 17.
We previously performed high throughput RNA-seq in paired eutopic and ectopic endometrial specimen of endometriosis patients, and validated the results by qRT-PCR in endometriosis endometrial tissues. MiR-96-5p was significantly downregulated in ectopic endometrial tissues compared to eutopic tissues. In order to identify the role of miR-96-5p in endometriosis and endometrial cells, and investigate the underlying mechanisms, the Ishikawa and End1/E6E7 cell lines were transfected with miR-96-5p mimics, miR-96-5p inhibitors or TGFBR1 siRNA. The expression of TGF-β/SMAD signaling pathway components and epithelial-mesenchymal transition (EMT) markers were examined by qRT-PCR and western blot, and cell viability and migration were determined by CCK-8, transwell and wound healing assays, respectively. We discovered miR-96-5p to be significantly downregulated while TGFBR1 was distinctly up-regulated in endometriosis. Overexpression of miR-96-5p inhibited endometrial cells viability and migration, while inhibition of miR-96-5p had opposite effect. Furthermore, we confirmed TGFBR1 was a direct target of miR-96-5p. Overexpression of miR-96-5p could block the TGF-β/SMAD signaling pathway via targeting TGFBR1 and reverse the TGF-β1 induced EMT in endometrial cell lines. In conclusion, we demonstrated that miR-96-5p interacted with TGF-β/SMAD signaling pathway and blocked the TGF-β1 induced EMT in endometrial cells via directly targeting TGFBR1.
我们之前在子宫内膜异位症患者的在位和异位子宫内膜标本中进行了高通量 RNA-seq 分析,并通过 qRT-PCR 在子宫内膜异位症子宫内膜组织中验证了这些结果。与在位组织相比,miR-96-5p 在异位子宫内膜组织中显著下调。为了确定 miR-96-5p 在子宫内膜异位症和子宫内膜细胞中的作用,并研究其潜在机制,我们用 miR-96-5p 模拟物、miR-96-5p 抑制剂或 TGFBR1 siRNA 转染 Ishikawa 和 End1/E6E7 细胞系。通过 qRT-PCR 和 Western blot 检测 TGF-β/SMAD 信号通路成分和上皮-间充质转化 (EMT) 标志物的表达,通过 CCK-8、transwell 和划痕愈合实验分别测定细胞活力和迁移。我们发现 miR-96-5p 在子宫内膜异位症中显著下调,而 TGFBR1 明显上调。miR-96-5p 的过表达抑制了子宫内膜细胞的活力和迁移,而 miR-96-5p 的抑制则产生相反的效果。此外,我们证实 TGFBR1 是 miR-96-5p 的直接靶标。miR-96-5p 的过表达可以通过靶向 TGFBR1 阻断 TGF-β/SMAD 信号通路,并逆转 TGF-β1 诱导的子宫内膜细胞系 EMT。总之,我们证明了 miR-96-5p 通过与 TGF-β/SMAD 信号通路相互作用,并通过直接靶向 TGFBR1 阻断 TGF-β1 诱导的子宫内膜细胞 EMT。