Micro-RNA miR-542-3p suppresses decidualization by targeting ILK pathways in human endometrial stromal cells

Xinlan Qu,Siying Zhuang,Yuanzhen Zhang,Yuan Fang

doi:10.1038/s41598-021-85295-2

Xinlan Qu, Siying Zhuang + Show 2 more

Open Access

https://doi.org/10.1038/s41598-021-85295-2

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Abstract

Decidualization of human endometrial stromal cells (HESCs) is a vital step for successful pregnancy. However, the process by which micro-RNAs (miRNAs) regulate decidualization remains elusive. Our current study was designed to identify the mechanism of miRNA miR-542-3p and its potential targets in regulating decidualization. The results showed that miR-542-3p was down-regulated in HESCs. Luciferase assay confirmed that integrin-linked kinase (ILK) is a direct target of miR-542-3p. Overexpression of miR-542-3p resulted in decreased ILK and downstream transforming growth factor β1 (TGF-β1) and SMAD family member 2 (SMAD2) expression. Additional expression of ILK attenuates the miR542-3p-induced down-regulation of TGF-β1 and SMAD2, changes properties such as suppression of proliferation and invasion, and induction of apoptosis, thereby affecting the differentiation of HESCs. Moreover, miR-542-3p overexpression caused down-regulation of the angiogenic factors vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2) and matrix metalloproteinase-9 (MMP-9), and the supernatant of HESCs overexpressing miR-542-3p inhibited the formation of tubular structures in human umbilical vein endothelial cells (HUVECs), suggesting that miR-542-3p inhibits angiogenesis of HUVECs. Furthermore, in our mouse model, following injection of miR-542-3p mimic into the endometrium of mice at pregnancy day 8 (D8), we found decreased miR-542-3p expression and loss of embryo implantation sites. In conclusion, miR-542-3p can affect the process of endometrial decidualization by down-regulating ILK. The present study adds further understanding of the process and regulation of decidualization.

Highlights

Embryo implantation refers to a continuous and complex dynamic biological process in which an activated blastocyst comes into contact with, and interacts with, the receiving endometrium
To verify if mir-542-3p expression is altered with decidualization, human endometrial stromal cells (HESCs) were treated with cAMP and MPA
We provide evidence to support an important role for miR-542-3p in endometrial decidualization

Summary

Introduction

Embryo implantation refers to a continuous and complex dynamic biological process in which an activated blastocyst comes into contact with, and interacts with, the receiving endometrium. MiRNAs can inhibit expression of the target gene, thereby affecting various biological processes such as cell differentiation, development, apoptosis and proliferation. These small miRNA molecules are stable, specific and sensitive, and are the main biological regulators of many fundamental physiological processes including reproduction. Recent studies have found that miRNAs play an important role in the regulation of pregnancy with many of the genes and proteins involved in endometrial receptivity and decidualization[5,6,7,8,9]. Studies have shown that miR-542-3p may inhibit the proliferation and differentiation of tumor cells by down-regulating the protein expression of survivin[12]. There is little research on the regulatory mechanisms of miR-542-3p related to endometrial decidualization, these processes are the focus of this study

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