MicroRNA-210 regulates human trophoblast cell line HTR-8/SVneo function by attenuating Notch1 expression: Implications for the role of microRNA-210 in pre-eclampsia

Mol Reprod Dev. 2019 Jul;86(7):896-907. doi: 10.1002/mrd.23154. Epub 2019 May 21.

Abstract

Successful pregnancy depends on the precise regulation of extravillous trophoblast cell invasion ability. MicroRNA-210-3p (miR-210), which is increased in the placenta of pre-eclampsia. Furthermore, miR-210 could inhibit trophoblasts invasion and might act as a serum biomarker for pre-eclampsia. Previous studies have demonstrated that miR-210 regulates HUVEC (human umbilical vein endothelial cell)-mediated angiogenesis by regulating the NOTCH1 signaling pathway. Studies by our group have previously identified that NOTCH1 plays a positive role in regulating trophoblast functions. However, the miR-210/NOTCH1 signaling pathway in the regulation of trophoblasts and pre-eclampsia has not been characterized. Therefore, this study was conducted to investigate the role of miR-210 and its relationship with NOTCH1 in trophoblasts. We first examined the expression levels of miR-210 and NOTCH1 in pre-eclamptic and normals placentas. Next, the expression and location of miR-210 and NOTCH1 in the first-trimester villi, maternal decidua, and placenta of late pregnancy were shown via in situ hybridization and immunohistochemistry. The trophoblast cell line HTR-8/SVneo was used to investigate the effects of miR-210 on the expression of NOTCH1 and cell bioactivity by upregulation and downregulation strategies. The results showed that miR-210 expression was increased, whereas NOTCH1 expression was decreased in pre-eclamptic placenta compared with controls. Upregulation of miR-210 decreased NOTCH1 expression, impaired HTR-8/SVneo proliferation, migration, invasion, and tube-like formation capabilities, and promoted apoptosis. In contrast, downregulation of miR-210 resulted in the opposite effects. These findings suggested that miR-210 might act as a contributor to trophoblast dysfunction by attenuating NOTCH1 expression.

Keywords: NOTCH1; microRNA-210; pre-eclampsia; trophoblast.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Apoptosis / genetics
  • Cell Line
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Down-Regulation
  • Female
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Placenta / metabolism
  • Pre-Eclampsia / metabolism*
  • Pre-Eclampsia / pathology
  • Pregnancy
  • Pregnancy Trimester, First / metabolism
  • Receptor, Notch1 / metabolism*
  • Transfection
  • Trophoblasts / metabolism*
  • Up-Regulation

Substances

  • MIRN210 microRNA, human
  • MicroRNAs
  • NOTCH1 protein, human
  • Receptor, Notch1