This study aims to identify the effect of miR-146a-5p on trophoblast cell invasion as well as the mechanism in preeclampsia (PE). Expression levels of miR-146a-5p and Wnt2 in preeclamptic and normal placentae were quantified. Trophoblast cells (HTR-8) were separately transfected with miR-146a-5p mimic, miR-146a-5p inhibitor, pcDNA3.1-Wnt2 or sh-Wnt2, and then the expression levels of miR-146a-5p, Wnt2, and epithelial-mesenchymal transition (EMT)-related proteins (Vimentin, N-cadherin and E-cadherin) were measured. Moreover, the proliferative, migratory and invasive capacities of trophoblast cells were detected, respectively. Dual luciferase reporter assay determined the binding of miR-146a-5p and Wnt2. Compared with normal placental tissues, the placentae from PE patients showed higher miR-146a-5p expression and lower Wnt2 expression. Transfection of miR-146a-5p inhibitor or pcDNA3.1-Wnt2 exerted pro-migratory and pro-invasive effects on HTR-8 cells and encouraged EMT in HTR-8 cells; transfection with miR-146a-5p mimic or sh-Wnt2 weakened the proliferative, migratory and invasive capacities as well as reduced EMT process of HTR-8 cells. Moreover, Wnt2 overexpression could partially counteract the suppressive effects of miR-146a-5p overexpression on the progression and EMT of HTR-8 cells. miR-146a-5p mediates trophoblast cell proliferation and invasion through regulating Wnt2 expression.

中文翻译：

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miR-146a-5p 介导的对子痫前期滋养层细胞进展和上皮间质转化的抑制

本研究旨在确定 miR-146a-5p 对滋养层细胞侵袭的影响以及先兆子痫 (PE) 的机制。量化了先兆子痫和正常胎盘中 miR-146a-5p 和 Wnt2 的表达水平。分别用 miR-146a-5p mimic、miR-146a-5p inhibitor、pcDNA3.1-Wnt2 或 sh-Wnt2 转染滋养层细胞 (HTR-8)，然后检测 miR-146a-5p、Wnt2 和测量了上皮间质转化 (EMT) 相关蛋白（波形蛋白、N-钙粘蛋白和 E-钙粘蛋白）。此外，分别检测了滋养层细胞的增殖、迁移和侵袭能力。双荧光素酶报告基因测定确定了 miR-146a-5p 和 Wnt2 的结合。与正常胎盘组织相比，PE 患者胎盘中 miR-146a-5p 表达较高，Wnt2 表达较低。转染 miR-146a-5p 抑制剂或 pcDNA3.1-Wnt2 对 HTR-8 细胞产生促迁移和促侵袭作用，并促进 HTR-8 细胞中的 EMT；转染 miR-146a-5p mimic 或 sh-Wnt2 减弱了 HTR-8 细胞的增殖、迁移和侵袭能力，并减少了 EMT 过程。此外，Wnt2 过表达可以部分抵消 miR-146a-5p 过表达对 HTR-8 细胞进展和 EMT 的抑制作用。miR-146a-5p 通过调节 Wnt2 表达介导滋养层细胞增殖和侵袭。此外，Wnt2 过表达可以部分抵消 miR-146a-5p 过表达对 HTR-8 细胞进展和 EMT 的抑制作用。miR-146a-5p 通过调节 Wnt2 表达介导滋养层细胞增殖和侵袭。此外，Wnt2 过表达可以部分抵消 miR-146a-5p 过表达对 HTR-8 细胞进展和 EMT 的抑制作用。miR-146a-5p 通过调节 Wnt2 表达介导滋养层细胞增殖和侵袭。