Division of Pharmaceutics, Faculty of Pharmacy, Keio University, Minato-ku, Tokyo, 105-8512, Japan.
Division of Pharmaceutics, Faculty of Pharmacy, Keio University, Minato-ku, Tokyo, 105-8512, Japan.
Biochem Biophys Res Commun. 2021 Mar 19;545:132-137. doi: 10.1016/j.bbrc.2021.01.077. Epub 2021 Feb 3.
Inadequate trophoblast invasion and impaired trophoblast-induced vascular remodeling are features of preeclampsia. In this context, an angiogenesis-related microRNA, miR-126, is abnormally expressed in preeclampsia placentas, but its role in trophoblast development remains unclear. The purpose of this study was to investigate the roles of miR-126 in the proliferation, migration, and invasion processes of trophoblast cells using the human choriocarcinoma-derived JEG-3 cell line as a model. The mRNA expression profiling of JEG-3 cells with and without miR-126 overexpression, in combination with bioinformatics analysis, identified LIN28A as a putative target of miR-126. The results of real-time RT-PCR and luciferase assay were consistent with this idea. Overexpression of miR-126 in JEG-3 cells decreased the invasive ability of the cells without affecting proliferation or migration. The invasiveness of JEG-3 cells was significantly reduced to a similar extent by knockdown of LIN28A with siRNA and by miR-126-overexpression-induced downregulation of LIN28A, although the level of LIN28A protein was much lower in the siLIN28A-transfected cells. These results indicate that miR-126 suppresses JEG-3 cell invasion by targeting LIN28A, and suggest that miR-126-mediated downregulation of LIN28A might contribute to the onset/deterioration of preeclampsia.
滋养细胞侵袭不足和滋养细胞诱导的血管重塑受损是子痫前期的特征。在这种情况下,一种与血管生成相关的 microRNA,miR-126,在子痫前期胎盘异常表达,但它在滋养细胞发育中的作用尚不清楚。本研究旨在以人绒毛膜癌细胞系 JEG-3 为模型,探讨 miR-126 在滋养细胞增殖、迁移和侵袭过程中的作用。结合生物信息学分析,对 JEG-3 细胞中有无 miR-126 过表达的 mRNA 表达谱进行了分析,鉴定出 LIN28A 是 miR-126 的一个潜在靶标。实时 RT-PCR 和荧光素酶检测结果与这一观点一致。在 JEG-3 细胞中过表达 miR-126 可降低细胞的侵袭能力,而不影响增殖或迁移。用 siRNA 敲低 LIN28A 和 miR-126 过表达下调 LIN28A 均可显著降低 JEG-3 细胞的侵袭能力,尽管 siLIN28A 转染细胞中的 LIN28A 蛋白水平要低得多。这些结果表明,miR-126 通过靶向 LIN28A 抑制 JEG-3 细胞侵袭,提示 miR-126 介导的 LIN28A 下调可能导致子痫前期的发生/恶化。