miR-21a inhibits decidual cell apoptosis by targeting Pdcd4

Abstract

Decidualization of endometrial stromal cells (ESCs) accompanied with embryo implantation is a key process in mammalian reproduction. Evidence suggests that maintenance of decidual cells function is essential. As a critical part in post-transcriptional gene regulation, microRNAs (miRNAs/miR) have been confirmed to be involved in decidualization. However, whether microRNAs regulate decidual cells function has not been reported. Aiming to clarify the role and potential mechanism of miRNAs in decidual cells, artificial induced decidualization model in mice was established. There are 94 differentially expressed miRNAs (≥two-fold change) between decidualized and non-decidualized tissues, including 60 upregulated and 34 downregulated miRNAs. Of the differentially expressed miRNAs, mmu-miR-21a is up-regulated. RT-qPCR also confirmed the up-regulation of mmu-miR-21a following decidualization in vivo and in vitro , and bioinformatic analysis and luciferase activity assay revealed Pdcd4 to be the target gene of mmu-miR-21a. Inhibition of mmu-miR-21a restrained secretory function of decidual cells induced by mESCs, accompanied with increase of Pdcd4 expression and resulted in the increase of cell apoptosis. In addition, we also determined the expression of hsa-miR-21 and Pdcd4 in human proliferative endometrial tissues and decidua tissues. hsa-miR-21 showed higher expression in human decidua tissues compared with proliferative endometrial tissues, while expression of Pdcd4 was contrary to that of hsa-miR-21. Similarly, cell apoptosis increased significantly in human endometrial stromal cell line in response to inhibition of hsa-miR-21. Collectively, we conclude that mmu-miR-21a/hsa-miR-21 may play a key role in regulating the function of decidual cells by inhibiting cell apoptosis through targeting Pdcd4.

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

“…[ 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 ] Li et al [ 12 ] found that miR-21a was elevated in human or mouse decidua tissues compared with endometrial tissues, which could inhibit DC apoptosis through targeting programmed cell death 4 ( Pdcd4 ). In addition, it was found that downregulated miR-346, and miR-582-3p in human placental tissues increased the migration and invasion of trophoblast cells in early pregnancy by promoting the expression of matrix metalloproteinase (MMP)-2 and MMP9 .…”

Macrophage polarization in spinal cord injury repair and the possible role of microRNAs: A review

“…Identifying miR-21 targets has aided in understanding its mechanisms of action in the immune response. MiR-21 targets the pro-inflammatory tumor suppressor Programmed Cell Death 4 (PDCD4) after LPS stimulation, regulating IL-10 induction, and the miR-21/PDCD4 axis also is a key target in various immunological diseases [ 157 , 158 ]. MiR-21 has a role in the pathophysiology of SCI, and its expression increased following the damage, peaking on the first day and then declining [ 159 ].…”

Developing In Vitro Models of Human Embryonic Aneuploidy

“…The Pdcd4 gene encodes for a protein (programmed cell death 4) that is an inhibitor of apoptosis and is conserved across mammalian species (Li et al, 2021). Within the human endometrium, Pdcd4 expression has been identified within proliferative endometrial cells and the decidua .…”