Ssc-miR-21-5p regulates endometrial epithelial cell proliferation, apoptosis and migration via the PDCD4/AKT pathway

J Cell Sci. 2020 Dec 9;133(23):jcs248898. doi: 10.1242/jcs.248898.

Abstract

Endometrial receptivity plays a vital role in successful embryo implantation in pigs. MicroRNAs (miRNAs), known as regulators of gene expression, have been implicated in the regulation of embryo implantation. However, the role of miRNAs in endometrial receptivity during the pre-implantation period remains elusive. In this study, we report that the expression level of Sus scrofa (ssc)-miR-21-5p in porcine endometrium tissues was significantly increased from day 9 to day 12 of pregnancy. Knockdown of ssc-miR-21-5p inhibited proliferation and migration of endometrial epithelial cells (EECs), and induced their apoptosis. We verified that programmed cell death 4 (PDCD4) was a target gene of ssc-miR-21-5p. Inhibition of PDCD4 rescued the effect of ssc-miR-21-5p repression on EECs. Our results also revealed that knockdown of ssc-miR-21-5p impeded the phosphorylation of AKT (herein referring to AKT1) by targeting PDCD4, which further upregulated the expression of Bax, and downregulated the levels of Bcl2 and Mmp9. Furthermore, loss of function of Mus musculus (mmu)-miR-21-5p in vivo resulted in a decreased number of implanted mouse embryos. Taken together, knockdown of ssc-miR-21-5p hampers endometrial receptivity by modulating the PDCD4/AKT pathway.

Keywords: AKT; Embryo implantation; Endometrial epithelial cells; PDCD4; Ssc-miR-21-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Cell Proliferation / genetics
  • Endometrium
  • Female
  • Mice
  • MicroRNAs* / genetics
  • Pregnancy
  • Proto-Oncogene Proteins c-akt* / genetics
  • Swine

Substances

  • MicroRNAs
  • Proto-Oncogene Proteins c-akt