Benzo[a]Pyrene-7, 8-Diol-9, 10-Epoxide Suppresses the Migration and Invasion of Human Extravillous Trophoblast Swan 71 Cells Due to the Inhibited Filopodia Formation and Down-Regulated PI3K/AKT/CDC42/PAK1 Pathway Mediated by the Increased miR-194-3p

Toxicol Sci. 2018 Nov 1;166(1):25-38. doi: 10.1093/toxsci/kfy182.

Abstract

Proper migration and invasion of trophoblast cells into endometrium is vital for successful embryo implantation during early pregnancy. Benzo[a]pyrene-7, 8-diol-9, 10-epoxide (BPDE) is an ultimate carcinogenic product of benzo[a]pyrene (BaP), which causes multiple trophoblast-related diseases. However, the mechanism of BPDE-inhibited migration/invasion of trophoblast cells is still unclear. In this work, we found that BPDE significantly inhibited the filopodia formation and migration/invasion of human trophoblast Swan 71 cells. BPDE up-regulated the level of miR-194-3p, which further inhibited the phosphoinositide 3-kinase (PI3K)/AKT/ cell division cycle 42/ p21 (RAC1) activated kinase 1 signaling pathway and depressed the filophdia formation of Swan71 cells. Addition of 740 Y-P, the activator of phosphoinositide 3-kinase, could stimulate cell migration/invasion, confirming the involvement of this pathway. Knock-down of miR-194-3p up-regulated this pathway and promoted filopodia formation and migration/invasion. Conversely, overexpression of miR-194-3p down-regulated this pathway and inhibited cell migration/invasion. Therefore, miR-194-3p takes important roles in the BPDE-inhibited filopodia formation and cell migration/invasion, providing valuable information in the BPDE-induced dysfunctions of human extravillous trophoblast cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / toxicity*
  • Cell Line
  • Cell Movement / drug effects*
  • Down-Regulation
  • Female
  • Humans
  • MicroRNAs / metabolism*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Pseudopodia / drug effects*
  • Pseudopodia / metabolism
  • Pseudopodia / pathology
  • Signal Transduction / drug effects*
  • Trophoblasts / drug effects*
  • Trophoblasts / metabolism
  • Trophoblasts / pathology
  • Up-Regulation
  • cdc42 GTP-Binding Protein / metabolism
  • p21-Activated Kinases / metabolism

Substances

  • MIRN194 microRNA, human
  • MicroRNAs
  • 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide
  • Phosphatidylinositol 3-Kinases
  • PAK1 protein, human
  • Proto-Oncogene Proteins c-akt
  • p21-Activated Kinases
  • CDC42 protein, human
  • cdc42 GTP-Binding Protein