HLA-G regulates the invasive properties of JEG-3 choriocarcinoma cells by controlling STAT3 activation

Placenta. 2013 Nov;34(11):1044-52. doi: 10.1016/j.placenta.2013.07.070. Epub 2013 Sep 17.

Abstract

The expression of human leucocyte antigen-G (HLA-G) in trophoblasts plays a crucial role in successful embryonic implantation, and reduced HLA-G expression might contribute to adverse obstetric outcomes. In this study, we silenced HLA-G expression using RNA interference in JEG-3 cells, resulting in a notably attenuated invasion capacity of the cells in a Transwell assay; however, no alterations in cell proliferation or apoptosis were observed. The down-regulation of HLA-G dampened the activation of signal transducer and activator of transcription 3 (STAT3), whereas the up-regulation of HLA-G promoted STAT3 activation and invasion in JEG-3 cells treated with human galectin-1. Most importantly, interleukin-6 (IL-6), but not galectin-1, was shown to rescue invasion deficiency in a dose-dependent manner. Thus, we demonstrate that HLA-G is able to regulate JEG-3 cell invasion by influencing STAT3 activation, which may underlie the implantation defects accompanying HLA-G hypo-expression in pre-eclampsia.

Keywords: HLA-G; Human galectin-1; IL-6; JEG-3; STAT3; Trophoblast invasion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Movement
  • Choriocarcinoma / metabolism*
  • Choriocarcinoma / pathology
  • Down-Regulation*
  • Embryo Implantation
  • Female
  • Galectin 1 / genetics
  • Galectin 1 / metabolism
  • HLA-G Antigens / chemistry
  • HLA-G Antigens / genetics
  • HLA-G Antigens / metabolism*
  • Humans
  • Interleukin-6
  • Neoplasm Invasiveness
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • RNA Interference
  • RNA, Messenger / metabolism
  • RNA, Small Interfering
  • Recombinant Proteins / metabolism
  • STAT3 Transcription Factor / agonists
  • STAT3 Transcription Factor / metabolism*
  • Trophoblasts / cytology
  • Trophoblasts / metabolism*
  • Trophoblasts / pathology
  • Up-Regulation
  • Uterine Neoplasms / metabolism*
  • Uterine Neoplasms / pathology

Substances

  • Galectin 1
  • HLA-G Antigens
  • IL6 protein, human
  • Interleukin-6
  • LGALS1 protein, human
  • Neoplasm Proteins
  • RNA, Messenger
  • RNA, Small Interfering
  • Recombinant Proteins
  • STAT3 Transcription Factor
  • STAT3 protein, human