miR-520 promotes DNA-damage-induced trophoblast cell apoptosis by targeting PARP1 in recurrent spontaneous abortion (RSA)

Gynecol Endocrinol. 2017 Apr;33(4):274-278. doi: 10.1080/09513590.2016.1266476. Epub 2016 Dec 31.

Abstract

The establishment and maintenance of successful pregnancy mainly depends on trophoblast cells. Their dysfunction has been implicated in recurrent spontaneous abortion (RSA), a major complication of pregnancy. However, the underlying mechanisms of trophoblasts dysfunction remain unclear. DNA-damage-induced cell apoptosis has been reported to play a vital role in cell death. In this study, we identified a novel microRNA (miR-520) in RSA progression via regulating trophoblast cell apoptosis. Microarray analysis showed that miR-520 was highly expressed in villus of RSA patients. By using flow cytometry analysis, we observed miR-520 expression was correlated with human trophoblast cell apoptosis in vitro, along with decreased poly (ADP-ribose) polymerase-1 (PARP1) expression. With the analysis of clinic samples, we observed that miR-520 level was negatively correlated with PARP1 level in RSA villus. In addition, overexpression of PARP1 restored the miR-520-induced trophoblast cell apoptosis in vitro. The status of chromosome in trophoblast implied that miR-520-promoted DNA-damage-induced cell apoptosis to regulate RSA progression. These results indicated that the level of miR-520 might associate with RSA by prompting trophoblast cell apoptosis via PARP1 dependent DNA-damage pathway.

Keywords: Apoptosis; DNA damage; PARP1; RSA; microRNA-520; recurrent spontaneous abortion; trophoblast.

MeSH terms

  • Abortion, Habitual / genetics
  • Abortion, Habitual / metabolism*
  • Adult
  • Apoptosis / physiology*
  • DNA Damage*
  • Female
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Poly (ADP-Ribose) Polymerase-1 / genetics
  • Poly (ADP-Ribose) Polymerase-1 / metabolism*
  • Pregnancy
  • Trophoblasts / cytology
  • Trophoblasts / metabolism*
  • Young Adult

Substances

  • MIRN520 microRNA, human
  • MicroRNAs
  • PARP1 protein, human
  • Poly (ADP-Ribose) Polymerase-1