MiR-543 Inhibits the Migration and Epithelial-To-Mesenchymal Transition of TGF-β-Treated Endometrial Stromal Cells via the MAPK and Wnt/β-Catenin Signaling Pathways

Abstract

Intrauterine adhesion (IUA) is one of the most prevalent reproductive system diseases in females. MicroRNAs (miRNAs) are reported to be master regulators in a variety of diseases, including IUA, but the role of microRNA-543 (miR-543) in IUA remains to be elucidated. In this study, we observed that miR-543 was downregulated in transforming growth factor-beta (TGF-β)-treated endometrial stromal cells (ESCs). Functionally, we observed that miR-543 suppressed the migration, epithelial-to-mesenchymal transition (EMT), and inhibited expression of extracellular matrix (ECM) proteins in TGF-β-treated ESCs. Mechanistically, MAPK1 is targeted by miR-543 after prediction and screening. A luciferase reporter assay demonstrated that miR-543 complementarily binds with the 3′ untranslated region of mitogen-activated protein kinase 1 (MAPK1), and western blot analysis indicated that miR-543 negatively regulates MAPK1 protein levels. In addition, results from rescue assays showed that miR-543 inhibits the migration and EMT of TGF-β-treated ESCs by targeting MAPK1. In addition, we observed that miR-543 inactivates the Wnt/β-catenin signaling pathway through inhibiting the phosphorylation of MAPK1 and β-catenin. Finally, we confirmed that miR-543 represses migration, EMT and inhibits levels of ECM proteins in TGF-β-treated ESCs by targeting the Wnt/β-catenin signaling pathway. Our results demonstrated that miR-543 suppresses migration and EMT of TGF-β-treated ESCs by targeting the MAPK and Wnt/β-catenin pathways.

Role of noncoding RNA in the pathophysiology and treatment of intrauterine adhesion

“…Moreover, many studies have shown that this pathway is involved in regulating the phenotype of endometrial stromal cells ( Zhou et al, 2019a ; Lv et al, 2020 ). Wang et al showed that miRNA-543 inhibits Wnt/β- Catenin pathway by targeting MAPK and therefore inhibits ECM protein level and the EMT process ( Wang et al, 2021 ). This experiment verified that miRNA-543 is considerably lowly expressed in TGF-β-treated embryonic stem cells (ESCs), and its anti-fibrosis effect was verified functionally.…”

The synergistic effect of bone marrow mesenchymal stem cells combined with estrogen on repairing rabbit endometrial injury and inhibiting EMT via Wnt/β-catenin pathway

“…Previous studies have demonstrated that Wnt/β-catenin signaling pathway is closely related to EMT in endometrial brosis [32,33]. In our rabbit model of IUA, we found that compared to the Sham operation group, the expression of core molecules in Wnt/β-catenin pathway was increased signi cantly in BMSCs combined with estrogen treated group, suggesting that the combination of BMSCs with estrogen inhibiting EMT partly through activating the Wnt/β-catenin pathway.…”

Bone marrow mesenchymal stem cells combined with estrogen synergistically promote endometrial regeneration and reverse EMT via Wnt/β-catenin signaling pathway

“…Hence, we also explored the synergistic effect of BMSCs combined with estrogen on EMT, and results indicated that the expression of epithelial markers was increased and interstitial markers was decreased in the combination therapy group, indicating that BMSCs/estrogen can promote re-epithelization through reverse EMT occurrence. Previous studies have demonstrated that Wnt/β-catenin signaling pathway is closely related to EMT in endometrial fibrosis [ 32 , 33 ]. So we studied the functions and mechanisms of Wnt signaling in IUA treatment with BMSCs transplantation.…”