Regulation of miR-101/miR-199a-3p by the epithelial sodium channel during embryo implantation: Involvement of CREB phosphorylation

Xiao Sun, Yechun Ruan, Jinghui Guo, Hui Chen, Lai Ling Tsang, Xiaohu Zhang, Xiaohua Jiang, Hsiao Chang Chan

Research output: Journal article publicationJournal articleAcademic researchpeer-review

25 Citations (Scopus)

Abstract

In our previous study, we have demonstrated that the epithelial sodium channel (ENaC) mediates the embryo-derived signals leading to the activation of CREB and upregulation of cyclooxygenase type 2 (COX2) required for embryo implantation. This study aims to investigate whether microRNAs (miRNAs) are involved in the ENaC-induced upregulation of COX2 during embryo implantation. The results show that the levels of miR-101 and miR-199a-3p, two COX2 targeting miRNAs, are reduced by ENaC activation, and increased by ENaC inhibition or knock-down of ENaC subunit (ENaCα ) in human endometrial surface epithelial (HES) cells or in mouse uteri during implantation. Phosphorylation of CREB is induced by the activation of ENaC, and blocked by ENaC inhibition or knockdown in HES cells. Knockdown of ENaCα or CREB in HES cells or in mouse uterus in vivo results in increases in miR-101 and miR-199a-3p, accompanied with decreases in COX2 protein levels and reduction in implantation rate. The downregulation of COX2 caused by knockdown of ENaC or CREB can be recovered by the inhibitors of miR-101 or miR-199a-3p in HES cells. These results reveal a novel molecular mechanism modulating COX2 expression during embryo implantation via ENaC-dependent CREB activation and COX2-targeting miRNAs.
Original languageEnglish
Pages (from-to)559-568
Number of pages10
JournalReproduction
Volume148
Issue number6
DOIs
Publication statusPublished - 1 Dec 2014
Externally publishedYes

ASJC Scopus subject areas

  • Reproductive Medicine
  • Embryology
  • Endocrinology
  • Obstetrics and Gynaecology
  • Cell Biology

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