Department of Obstetrics and Gynecology, Xi'an Fourth Hospital, Shanxi, China.
Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Reproduction. 2020 Jul;160(1):21-29. doi: 10.1530/REP-19-0614.
A successful pregnancy crucially depends on well-regulated extravillous trophoblast migration and invasion. Maternally expressed gene 3 (MEG3) is a long noncoding RNA that plays an important role in regulating trophoblast cells cell function. As previously reported, the expression of MEG3 was reduced in preeclampsia, and downregulation of MEG3 could suppress trophoblast cells migration and promote its apoptosis. However, the downstream regulatory mechanism of MEG3 remains unknown. As reported, MEG3 could inhibit cell proliferation in endometrial carcinoma by regulating Notch signaling. Our previous studies have demonstrated that Notch1 is downregulated in preeclampsia and that inhibiting the expression of Notch1 could promote trophoblast cell apoptosis. Therefore, this study was designed to investigate the role of MEG3 and its the relationship with Notch1 in trophoblasts. In this study, the mRNA expression levels of both MEG3 and Notch1 were decreased in preeclampsia placenta (n = 15) compared to the normal samples (n = 15). Exogenous upregulation and downregulation of MEG3 in HTR8/SVneo cells were performed to investigate the role of MEG3 in cell biological behavior and its effects on Notch1 expression. The results showed that MEG3 enhancement promoted trophoblast cell migration and invasion and inhibited cell apoptosis. Downregulation of MEG3 elicited the opposite results. Associated factors, such as matrix metalloproteinases 2 (MMP2), BAX, and Bcl-2, were examined at the mRNA and protein levels. Our study demonstrated that MEG3 could regulate Notch1 expression to modulate trophoblast cell migration, invasion, and apoptosis, which may represent the molecular mechanism of poor placentation during preeclampsia.
成功的妊娠取决于绒毛外滋养细胞的迁移和浸润的良好调控。母源性表达基因 3(MEG3)是一种长链非编码 RNA,在调节滋养细胞功能方面发挥着重要作用。据先前报道,子痫前期中 MEG3 的表达减少,而 MEG3 的下调可抑制滋养细胞迁移并促进其凋亡。然而,MEG3 的下游调控机制尚不清楚。据报道,MEG3 通过调节 Notch 信号通路抑制子宫内膜癌中的细胞增殖。我们之前的研究表明,Notch1 在子痫前期中下调,抑制 Notch1 的表达可促进滋养细胞凋亡。因此,本研究旨在探讨 MEG3 及其与 Notch1 在滋养细胞中的作用及其关系。在这项研究中,与正常样本(n=15)相比,子痫前期胎盘(n=15)中 MEG3 和 Notch1 的 mRNA 表达水平均降低。在 HTR8/SVneo 细胞中外源性上调和下调 MEG3,以研究 MEG3 在细胞生物学行为中的作用及其对 Notch1 表达的影响。结果表明,MEG3 的增强促进了滋养细胞的迁移和侵袭,并抑制了细胞凋亡。MEG3 的下调则产生了相反的结果。还在 mRNA 和蛋白水平上检测了相关因子,如基质金属蛋白酶 2(MMP2)、BAX 和 Bcl-2。我们的研究表明,MEG3 可以通过调节 Notch1 的表达来调节滋养细胞的迁移、侵袭和凋亡,这可能代表了子痫前期中胎盘不良形成的分子机制。