Pristimerin Suppresses Trophoblast Cell Epithelial-Mesenchymal Transition via miR-542-5p/EGFR Axis

Drug Des Devel Ther. 2020 Nov 2:14:4659-4670. doi: 10.2147/DDDT.S274595. eCollection 2020.

Abstract

Background: Ectopic pregnancy (EP) is an ectopic embryo implantation occurred outside the uterine cavity. Nowadays, more attention have garnered in fast and effective treatment with less side effects. Pristimerin is known as the clinical application for anti-cancer, and the effect on EP therapy is still unclear.

Materials and methods: Trophoblast cell line HTR-8/SVneo was used; then, we performed cell counting kit-8 assay, wound healing assay, flow cytometry and real-time polymerase chain reaction analysis (RT-PCR) to detect the cell viability, migration ability, apoptosis and epithelial-mesenchymal transition (EMT) under pristimerin treatment. In addition, public bioinformatic database was used to discover the connection between molecular and genes. Finally, we used miRNA transfection and RT-PCR techniques to determine the underlying molecular mechanism.

Results: We revealed that pristimerin inhibited trophoblast cells proliferation, migration and EMT, while induced trophoblast cell apoptosis. Furthermore, expression of miR-542-5p, AGO2 and EGFR was suppressed in HTR-8/SVneo cells post pristimerin treatment, and miR-542-5p silence showed the same effect. Combing pristimerin treatment and miR-542-5p silence showed a synergistic action.

Conclusion: Pristimerin could be an effective treatment to block embryo implantation by miR-542-5p and EGFR down-regulation.

Keywords: EGFR; miR-542-5p; pristimerin; trophoblast cell; unruptured ectopic pregnancy.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Epithelial-Mesenchymal Transition / drug effects*
  • ErbB Receptors / antagonists & inhibitors*
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism
  • Female
  • Injections, Intraperitoneal
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / antagonists & inhibitors*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Molecular Structure
  • Pentacyclic Triterpenes / administration & dosage
  • Pentacyclic Triterpenes / pharmacology*
  • Signal Transduction / drug effects
  • Structure-Activity Relationship
  • Trophoblasts / drug effects*
  • Trophoblasts / metabolism

Substances

  • MIRN542 microRNA, mouse
  • MicroRNAs
  • Pentacyclic Triterpenes
  • celastrol methyl ester
  • EGFR protein, mouse
  • ErbB Receptors

Grants and funding

The research is supported by grant from NSFC (81671592), Finance Department of Jilin Province (JLSWSRCZX2020-089), Education Department of Jilin Province (JJKH20201064KJ), and Science and Technology Department of Jilin Province (20180201028YY).