Yu Lin, Kuang Li-Yun, He Fang, Du Li-Li, Li Qiu-Lian, Sun Wen, Zhou Yan-Mei, Li Xiao-Mei, Li Xiu-Ying, Chen Dun-Jin
1 Key Laboratory for Major Obstetric Diseases of Guangdong Province, Department of Obstetrics and Gynecology, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Reprod Sci. 2018 Dec;25(12):1619-1628. doi: 10.1177/1933719117749753. Epub 2018 Jan 23.
A growing body of evidence suggests that the dysregulation of long noncoding RNA is increasingly linked to many human diseases. Maternally expressed gene 3 ( MEG3) is one such gene thought to be affected. In the placenta of patients with preeclampsia, there is reduced expression of MEG3; however, its role and the mechanism involved are not clear. Therefore, we examined the expression of MEG3, epithelial-mesenchymal transition (EMT) markers (E-cadherin and N-cadherin), and TGF-β/smad signaling pathway genes ( TGF-β1, smad3, and smad7) in the placental tissues of 20 patients with preeclampsia and 20 healthy patients. We further observed the impact of MEG3 on the invasion and migration functions of human trophoblast cells and the effects on EMT and TGF-β/smad signaling pathways in an Human trophoblast cell-8 (HTR-8)Vneo cell line. The expression of MEG3 was lower in tissues from patients with preeclampsia having an EMT decline, as well as a messenger RNA expression of smad7. The expression of TGF-β1 and smad3 were higher in patients with preeclampsia. In HTR-8/SVneo cells with overexpressed MEG3, the invasion and migration functions were enhanced and accompanied by higher EMT and a significantly increased expression of smad7. Our data indicate that MEG3 is closely associated with the pathogenesis of preeclampsia and thus associated with changes in the EMT of placental trophoblast cells. These results indicate that MEG3 regulation of trophoblast cell EMT via the TGF-β pathway inhibitor smad7 may be the molecular mechanism involved in the pathogenesis of preeclampsia.
越来越多的证据表明，长链非编码RNA的失调与许多人类疾病的关联日益紧密。母源表达基因3（MEG3）就是这样一个被认为受到影响的基因。在子痫前期患者的胎盘中，MEG3的表达降低；然而，其作用及相关机制尚不清楚。因此，我们检测了20例子痫前期患者和20例健康患者胎盘组织中MEG3、上皮-间质转化（EMT）标志物（E-钙黏蛋白和N-钙黏蛋白）以及TGF-β/smad信号通路基因（TGF-β1、smad3和smad7）的表达。我们进一步观察了MEG3对人滋养层细胞侵袭和迁移功能的影响，以及对人滋养层细胞-8（HTR-8）Vneo细胞系中EMT和TGF-β/smad信号通路的作用。子痫前期患者组织中MEG3的表达较低，同时伴有EMT下降以及smad7的信使核糖核酸表达降低。子痫前期患者中TGF-β1和smad3的表达较高。在MEG3过表达的HTR-8/SVneo细胞中，侵袭和迁移功能增强，并伴有更高的EMT以及smad7表达显著增加。我们的数据表明，MEG3与子痫前期的发病机制密切相关，因此与胎盘滋养层细胞的EMT变化有关。这些结果表明，MEG3通过TGF-β途径抑制剂smad7调节滋养层细胞EMT可能是子痫前期发病机制中的分子机制。
