miR-144 may regulate the proliferation, migration and invasion of trophoblastic cells through targeting PTEN in preeclampsia

Biomed Pharmacother. 2017 Oct;94:341-353. doi: 10.1016/j.biopha.2017.07.130. Epub 2017 Aug 1.

Abstract

Previous studies indicated that microRNAs (miRNAs) were aberrantly expressed in the placentas of patients with Preeclampsia (PE); however, the underlying mechanism still requires further investigation. The aim of this study is to investigate the roles of miR-144 in preeclampsia and the related mechanism. The expression of miR-144 and PTEN in 30 placentas of patients with PE and 30 normal placentas was compared; next, HTR8/SVneo cells were transfected with miR-144 mimics and miR-144 inhibitors and cultured for 48h, and the proliferation and apoptosis, cell migration and invasion of the cells were examined; furthermore, the expression PTEN, Caspase-3 and Bcl-2 was examined; next, dual luciferase reporter assay has been performed to confirm that PTEN is a direct target of miR-144; finally, HTR-8/SVneo cells were transfected with either PTEN overexpression plasmid or PTEN RNAi to determine whether knockdown or overexpression of PTEN can mimic the effect of miR-144 We have observed that the expression of miR-144 was significantly decreased and the expression of PTEN was markedly increased in placentas of patients with PE compared with normal placentas; moreover, transfection of miR-144 mimics in trophoblastic cells induced significant increase in cell proliferation, migration, invasion, and decrease in cell apoptosis, and also affected the cell cycles; on the other hand, transfection of miR-144 inhibitors has shown the opposite effects; furthermore, transient overexpression of miR-144 induced marked decrease in the expression of PTEN, Caspase-3 and increase in expression of Bcl-2 (P<0.01), while transfection of miR-144 inhibitors showed the opposite effects; finally, PTEN has been confirmed as a direct target of miR-144; finally, transfection of PTEN overexpression plasmid or PTEN RNAi can mimic the results of miR-144 inhibitor or miR-144 mimics, respectively. In conclusion, miR-144 was down-regulated in PE, and miR-144 may play important roles in the pathogenesis of PE through targeting PTEN in trophoblastic cells. These results suggested that miR-144 has the potential to become a therapeutic target for the treatment of PE.

Keywords: Migration; PTEN; Preeclampsia; Proliferation; miR-144.

MeSH terms

  • Adult
  • Apoptosis
  • Cell Line
  • Cell Movement*
  • Cell Proliferation*
  • Female
  • Gene Knockdown Techniques
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism*
  • Placenta / metabolism
  • Pre-Eclampsia / metabolism*
  • Pregnancy
  • Transfection
  • Trophoblasts / metabolism*

Substances

  • MIRN144 microRNA, human
  • MicroRNAs
  • PTEN Phosphohydrolase
  • PTEN protein, human