Department of Obstetrics, The Second Hospital of Hebei Medical University , Shijiazhuang , P.R. China.
Department of Obstetrics, The Fourth Hospital of Shijiazhuang , Shijiazhuang , P.R. China.
RNA Biol. 2019 Nov;16(11):1565-1573. doi: 10.1080/15476286.2019.1644591. Epub 2019 Jul 29.
Dysfunctions of epithelial-mesenchymal transition (EMT)-regulated cell migration and invasion have been involved in the pathogenesis of pre-eclampsia (PE). However, the role of circRNAs in EMT of PE has not been widely investigated. In this study, we identified that circTNRC18 was upregulated in PE placentas compared with normal pregnancy placentas. Moreover, circTNRC18 negatively regulated trophoblast cell migration and EMT. Overexpression of circTNRC18 reduced while depletion of circTNRC18 enhanced trophoblast cell migration and EMT. Mechanistically, circTNRC18 sponged miR-762 contributed to inhibit miR-762 activity and elevated EMT-related transcriptional factor Grhl2 protein level. miR-762 expression was lower in PE placentas and played a promoting role in trophoblast cell migration and EMT. In contrast, Grhl2 was highly expressed in PE placentas. Furthermore, we confirmed that upregulation of Grhl2 by circ-TNRC18-induced inhibition of miR-762 led to trophoblast cell migration and EMT. In conclusions, circTNRC18/miR-762/Grhl2 axis plays a key role in trophoblast cell migration and EMT. circTNRC18/miR-762/Grhl2 axis may be a potential therapeutic target in PE.
上皮-间充质转化（EMT）调节的细胞迁移和侵袭功能障碍与子痫前期（PE）的发病机制有关。然而，circRNAs 在 PE 的 EMT 中的作用尚未得到广泛研究。在本研究中，我们发现与正常妊娠胎盘相比，PE 胎盘circTNRC18 上调。此外，circTNRC18 负调控滋养细胞迁移和 EMT。circTNRC18 的过表达降低了而 circTNRC18 的耗竭增强了滋养细胞迁移和 EMT。机制上，circTNRC18 海绵吸附 miR-762 有助于抑制 miR-762 活性并提高 EMT 相关转录因子 Grhl2 蛋白水平。miR-762 在 PE 胎盘中的表达较低，在促进滋养细胞迁移和 EMT 中发挥作用。相反，Grhl2 在 PE 胎盘中高表达。此外，我们证实 circ-TNRC18 通过抑制 miR-762 引起的 Grhl2 上调导致滋养细胞迁移和 EMT。总之，circTNRC18/miR-762/Grhl2 轴在滋养细胞迁移和 EMT 中起关键作用。circTNRC18/miR-762/Grhl2 轴可能是 PE 的潜在治疗靶点。
