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

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.

Assessment of BMP7, SMAD4, and CDH1 Expression Profile and Regulatory miRNA-542-3p in Eutopic and Ectopic Endometrium of Women with Endometriosis

“…This result is important in terms of the ability of ectopic endometrial stromal cells to decidualize. It has been postulated that the overexpression of miR-542-3p inhibits the process of differentiation (decidualization) of endometriotic stromal cells [ 72 , 73 , 74 ] and the proliferation of human endometrial stromal cells [ 75 ]. An important result from our study is the observation of a positive, albeit statistically insignificant, correlation between miR-542-3p expression and the severity of the disease.…”

Impairment of Decidualization of Endometrial Stromal Cells by hsa-miR-375 Through NOX4 Targeting

“…miR-194-3p has also been reported to have a relationship with decidualization via the downregulation of PGR [ 29 ]. Recently, Qu et al have reported that miR-542-3p inhibits decidualization through the downregulation of the ILK pathway [ 30 ]. In our study, miR-375 was found to be a negative regulator of decidualization in HESCs.…”

Emerging role of miRNAs, lncRNAs, and circRNAs in pregnancy-associated diseases

“…Furthermore, many miRNAs’ functions were explored in pregnancy-related cellular and animal models. Downregulation of miR-542-3p in human ESCs facilitated ESCs decidualization by activating integrin-linked kinase ( ILK )/transforming growth factor (TGF)-β1/SMAD family member 2 signaling pathway and induced loss of embryo implantation in a mouse model of early pregnancy [10] . Conversely, a decreased expression of miRNA-155-5p in decidua tissue not only promoted proliferation but also inhibited apoptosis of decidua stromal cells by inhibiting the nuclear factor kappa B signaling pathway, which could maintain normal pregnancy [11] .…”