Department of Obstetrics and Gynecology, First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710061, China.
Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Placenta. 2021 Jun;109:64-71. doi: 10.1016/j.placenta.2021.04.016. Epub 2021 May 5.
Pre-eclampsia is characterized by insufficient spiral artery remodeling, and trophoblast dysfunction plays an important role in this process. Noncoding RNAs (microRNAs (miRNAs) and long noncoding RNAs (LncRNAs) are included) can regulate trophoblasts. MicroRNA-210 (miR-210) can decrease trophoblast cell migration and invasion and may act as a biomarker for preeclampsia. LncRNA maternally expressed gene 3 (MEG3) plays a positive role in pre-eclampsia, and MEG3 can be a downstream target of miR-210 in human umbilical vein endothelial cells (HUVEC). However, the effect of miR-210 on MEG3 and the mechanism of action of the miR-210/MEG3 axis in trophoblasts remain unclear.
The localization of miR-210 and MEG3 in the human placenta in early pregnancy was determined by in situ hybridization. Then, HTR8/SVneo cells were used to investigated the effect of miR-210 on MEG3 expression and biological activity of trophoblasts in the migration and invasion assays. Gain- and loss-of-function experiments were performed to determine the mechanism of action of miR-210 and MEG3 in Epithelial-mesenchymal transition (EMT) of HTR8/SVneo cells.
The qRT-PCR and western blotting results demonstrated that the upregulation of miR-210 decreases MEG3, N-cadherin and Vimentin expression and increases E-cadherin expression to inhibit EMT in HTR-8/SVneo cells. Inhibition of the expression of miR-210 results in the opposite effects. Gain- and loss-of-function assay indicated that miR-210 can impair the EMT, migration, and invasion of HTR8/SVneo cells by regulating the expression of MEG3.
MiR-210 may be a negative regulator of trophoblast EMT that acts by suppressing MEG3 expression.
子痫前期的特征是螺旋动脉重塑不足，滋养细胞功能障碍在此过程中起重要作用。非编码 RNA（微小 RNA（miRNAs）和长非编码 RNA（LncRNAs））可以调节滋养细胞。微小 RNA-210（miR-210）可以降低滋养细胞的迁移和侵袭能力，可能作为子痫前期的生物标志物。LncRNA 母源性表达基因 3（MEG3）在子痫前期中发挥积极作用，并且 MEG3 可以是人类脐静脉内皮细胞（HUVEC）中 miR-210 的下游靶标。然而，miR-210 对 MEG3 的影响以及 miR-210/MEG3 轴在滋养细胞中的作用机制尚不清楚。
通过原位杂交确定 miR-210 和 MEG3 在人早孕胎盘组织中的定位。然后，使用 HTR8/SVneo 细胞在迁移和侵袭实验中研究 miR-210 对 MEG3 表达和滋养细胞生物学活性的影响。进行增益和缺失功能实验，以确定 miR-210 和 MEG3 在 HTR8/SVneo 细胞上皮间质转化（EMT）中的作用机制。
qRT-PCR 和 Western blot 结果表明，miR-210 的上调降低了 MEG3、N-钙黏蛋白和波形蛋白的表达，增加了 E-钙黏蛋白的表达，从而抑制了 HTR-8/SVneo 细胞中的 EMT。抑制 miR-210 的表达则产生相反的效果。增益和缺失功能实验表明，miR-210 可以通过调节 MEG3 的表达来损害 HTR8/SVneo 细胞的 EMT、迁移和侵袭。
miR-210 可能是一种负调控滋养细胞 EMT 的因子，通过抑制 MEG3 的表达发挥作用。
