MiR-223-3p alleviates TGF-β-induced epithelial-mesenchymal transition and extracellular matrix deposition by targeting SP3 in endometrial epithelial cells.

Jian Gao,Di Shang,Pan Miao,Dongyan Sun,Yanling Chen,Zhihe Jiang

doi:10.1515/med-2022-0424

Abstract

Intrauterine adhesion (IUA) is the clinical manifestation of endometrial fibrosis. The dysregulation of microRNAs (miRNAs) has been confirmed to implicate in a diversity of human diseases, including IUA. Nevertheless, the specific function of miR-223-3p in IUA remains to be clarified. Reverse transcription quantitative polymerase chain reaction analysis displayed the downregulation of miR-223-3p in IUA tissues and endometrial epithelial cells (EECs). Results from wound healing assay, Transwell assay and western blotting showed that TGF-β facilitated the migration and invasion of EECs and induced epithelial-mesenchymal transition (EMT) process as well as extracellular matrix (ECM) deposition. Overexpression of miR-223-3p in EECs was shown to suppress the effects induced by TGF-β. Bioinformatics analysis and luciferase reporter assay revealed the binding relation between miR-223-3p and SP3. SP3 was highly expressed in IUA and its expression was inversely correlated with miR-223-3p expression in IUA tissue samples. Additionally, upregulation of SP3 reversed the influence of miR-223-3p on the phenotypes of EECs. In conclusion, miR-223-3p alleviates TGF-β-induced cell migration, invasion, EMT process and ECM deposition in EECs by targeting SP3.

Highlights

Intrauterine adhesion (IUA), characterized by endometrial fibrosis, is a uterine disease caused by trauma, infection, inflammation and other factors [1]
A previous study has confirmed that TGF-β stimulation enhances the expression of miR-223-3p in benign prostatic hyperplasia epithelial cells [23]
We investigated the impact of TGF-β in epithelial cells (EECs)

Summary

Introduction

Intrauterine adhesion (IUA), characterized by endometrial fibrosis, is a uterine disease caused by trauma, infection, inflammation and other factors [1]. Patients with IUA may suffer from pelvic pain, abnormal menstruation, recurrent abortion, infertility and pregnancy complications [2,3]. The main approach adopted for IUA treatment is transcervical resection of adhesions via hysteroscopy followed by re-adhesion prevention [4,5]. The recurrence rate after treatment is still high. It was reported that the recurrence rate of mild and moderate IUA is approximately 30% and that of severe cases is as high as 62.5% [6,7]. It is of great significance to find a better method to prevent adhesion formation

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