Progesterone-Induced miR-152 Inhibits the Proliferation of Endometrial Epithelial Cells by Downregulating WNT-1

Reprod Sci. 2017 Oct;24(10):1444-1453. doi: 10.1177/1933719116689595. Epub 2017 Jan 26.

Abstract

Progesterone (P4) is an important ovarian hormone that inhibits estrogen-dependent proliferation of endometrial epithelial cells (EECs). miR-152 has been reported to be a cell cycle regulator. In this study, we first demonstrated that P4 induced the expression of miR-152 in ovariectomized mice and Ishikawa cell. miR-152 was detected in the human endometrial cell lines that were stably transfected with P4 receptor. Results showed that P4 induced its expression through its receptor B subtype. Then, using the specific miRNA mimic and inhibitor, we proved that miR-152 impeded G1/S transition in the cell cycle of EECs and inhibited cellular proliferation via downregulating WNT-1 in mice and human endometrial cancer cell lines (Ishikawa, HEC-1-b, and KLE). miR-152 induced by P4 is an important inhibitor for the proliferation of EECs. miR-152 may be an important tumor suppressor microRNA in endometrial cancer.

Keywords: cellular proliferation; endometrial cancer cells; endometrial epithelial cells; miR-152; progesterone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Count
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Down-Regulation / drug effects*
  • Endometrium / drug effects*
  • Endometrium / metabolism
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Estradiol / pharmacology
  • Female
  • Humans
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Progesterone / pharmacology*
  • Signal Transduction / drug effects
  • Wnt1 Protein / genetics
  • Wnt1 Protein / metabolism*

Substances

  • MIRN152 microRNA, mouse
  • MicroRNAs
  • Wnt1 Protein
  • Progesterone
  • Estradiol