Department of Obstetrics, The First Hospital of China Medical University, Shenyang, China.
Cell Biochem Funct. 2020 Jun;38(4):472-479. doi: 10.1002/cbf.3492. Epub 2020 Jan 23.
Preeclampsia (PE) is a serious disease that occurs after 20 weeks during pregnancy. There are some aberrant microRNAs (miRNAs) that are associated with the etiology of PE. As discovered by scholars, there was an increased level of miR-215-5p in plasma of PE patients compared with the control group; nonetheless, there is still no knowledge of the mechanism of miR-215-5p in PE. We carried out the comparison of the expression levels of miR-215-5p, and the supposed target gene cell division cycle 6 (CDC6) in 30 placentas from PE patients as well as 30 placentas from normal pregnant women. The verification of the impacts of miR-215-5p and CDC6 was carried out by functional assays in HTR-8/SVneo cells transfected with the miR-215-5p mimic or siR-CDC6. As indicated by findings, miR-215-5p showed an apparent increase; conversely, CDC6 was inhibited in the experiment group. The upregulation of miR-215-5p inhibited both the migration and invasive potential of trophoblasts, besides decreasing the G1-S transition and downregulating CDC6 in HTR-8/SVneo cells; nonetheless, it did not significantly impact the cell proliferation. Furthermore, siR-CDC6 replicated the functions of the miR-215-5p mimic. Also, the miR-215-5p mimic and siR-CDC6 both decreased the epithelial-mesenchymal transition (EMT) with additional E-cadherin level and decreased the expressions of N-cadherin as well as vimentin in trophoblast cells. To conclude, miR-215-5p decreased not only the migration but also the invasion of trophoblasts through regulating CDC6, which indicated that miR-215-5p might be associated with the etiology of PE. SIGNIFICANCE OF THE STUDY: More and more attention has been paid on the roles of miRNAs in the pathogenesis of PE. However, there is no study of miR-215-5p in the etiology of PE. We first investigated the mechanism of miR-215-5p in placental tissues and HTR-8/SVneo cells. It was suggested that miR-215-5p decreased the abilities of migration and invasion of trophoblasts through regulating CDC6 in PE. miR-215-5p might be used as an target for the early diagnosis and treatment of PE in the future.
子痫前期(PE)是一种在怀孕 20 周后发生的严重疾病。一些异常的 microRNAs(miRNAs)与 PE 的病因有关。学者们发现,与对照组相比,PE 患者血浆中的 miR-215-5p 水平升高;然而,miR-215-5p 在 PE 中的作用机制仍不清楚。我们比较了 30 例 PE 患者和 30 例正常孕妇胎盘组织中 miR-215-5p 和假定靶基因细胞分裂周期蛋白 6(CDC6)的表达水平。通过转染 miR-215-5p 模拟物或 siR-CDC6 的 HTR-8/SVneo 细胞的功能测定验证了 miR-215-5p 和 CDC6 的影响。结果表明,实验组 miR-215-5p 明显升高,而 CDC6 受到抑制。miR-215-5p 的上调抑制了滋养细胞的迁移和侵袭能力,同时降低了 HTR-8/SVneo 细胞的 G1-S 过渡并下调了 CDC6;然而,它对细胞增殖没有显著影响。此外,siR-CDC6 复制了 miR-215-5p 模拟物的功能。miR-215-5p 模拟物和 siR-CDC6 均可降低上皮-间充质转化(EMT),增加上皮钙黏蛋白水平,并降低滋养细胞中 N-钙黏蛋白和波形蛋白的表达。总之,miR-215-5p 通过调节 CDC6 不仅降低了滋养细胞的迁移能力,还降低了其侵袭能力,表明 miR-215-5p 可能与 PE 的病因有关。研究的意义:越来越多的人关注 miRNAs 在子痫前期发病机制中的作用。然而,miR-215-5p 在子痫前期病因学中的研究尚属空白。我们首次研究了 miR-215-5p 在胎盘组织和 HTR-8/SVneo 细胞中的作用机制。提示 miR-215-5p 通过调节 CDC6 降低滋养细胞的迁移和侵袭能力。miR-215-5p 可能成为未来子痫前期早期诊断和治疗的新靶点。