miR-215-5p decreases migration and invasion of trophoblast cells through regulating CDC6 in preeclampsia

Cell Biochem Funct. 2020 Jun;38(4):472-479. doi: 10.1002/cbf.3492. Epub 2020 Jan 23.

Abstract

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.

Keywords: CDC6; EMT; miR-215-5p; placenta; preeclampsia.

MeSH terms

  • Adult
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Line
  • Cell Movement*
  • Female
  • G1 Phase*
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Pre-Eclampsia / genetics
  • Pre-Eclampsia / metabolism*
  • Pre-Eclampsia / pathology
  • Pregnancy
  • S Phase*
  • Trophoblasts / metabolism*
  • Trophoblasts / pathology

Substances

  • CDC6 protein, human
  • Cell Cycle Proteins
  • MIRN215 microRNA, human
  • MicroRNAs
  • Nuclear Proteins