MicroRNA-342 Promotes the Malignant-Like Phenotype of Endometrial Stromal Cells via Regulation of Annexin A2.

Dan Sun,Li Wang,Xin Guo,Yiting Wang,Hung Wei Pan

doi:10.1155/2021/1328682

Abstract

The relevance of miRNA- (miR-) 342 to endometriosis has been highlighted, while its function in regulating the malignant-like phenotype of endometrial stromal cells which demonstrate epigenetic abnormalities that alter expression of transcription factors, remains unclear. Therefore, we sought to characterize the effects of miR-342 in endometrial stromal cell proliferation by regulating Annexin A2 (ANXA2). We first characterized the levels of miR-342 and ANXA2 in 31 cases of normal endometrium from patients with grade II-III cervical intraepithelial neoplasia or patients with hysterectomy versus ectopic endometrial tissues of 42 patients with endometriosis. miR-342 was upregulated, while ANXA2 was downregulated in ectopic endometrial tissues. Bioinformatics website and dual-luciferase reporter assay revealed that miR-342 negatively modulated ANXA2 expression. Following loss- and gain-of-function approaches, CCK-8, Transwell, and flow cytometry demonstrated that overexpression of miR-342 markedly increased cell proliferation, migration, and invasion but inhibited cell apoptotic ratio of endometrial stromal cells, which was reversed by ANXA2 elevation. Further, overexpressed miR-342 activated the PI3K/AKT/mTOR signaling pathway, as evidenced by upregulated levels of p-PI3K/PI3K, p-AKT/AKT, and p-mTOR/mTOR. Taken together, miR-342 targets ANXA2 to activate the PI3K/AKT/mTOR signaling pathway, thereby promoting the malignant-like phenotype of endometrial stromal cells, highlighting miR-342 inhibition as a promising approach for the treatment of endometriosis.

Highlights

Endometriosis, a frequently chronic illness haunting young women, is characterized by the endometrial stroma existence and glands outside the normal endometrium, accompanied by painful symptoms [1]
The PI3K/AKT/mTOR pathway is mentioned in the literature on intracellular kinases activated by the endometriotic environment [13]. These findings indicated the relations between the PI3K/Akt/mTOR pathway and miR-342 as well as between the PI3K/Akt/mTOR pathway and endometrial stromal cell growth
Thirty-one cases of normal endometrial tissues from patients with grade II-III cervical intraepithelial neoplasia (CIN) or received hysterectomy were collected as controls

Summary

Introduction

Endometriosis, a frequently chronic illness haunting young women, is characterized by the endometrial stroma existence and glands outside the normal endometrium, accompanied by painful symptoms [1]. Endometrial stromal cells were used in this study as an in vitro model. A better understanding of the molecular activity in endometrial stromal cells could potentially contribute to novel nonhormonal treatments of endometriosis. MicroRNAs (miRNAs) serve as mediators of the gene expression and biomarkers for several diseases, including endometriosis [5]. MiR-342-3p with higher level was identified to be one of the miRNA biomarkers for endometriosis, which is conducive to earlier identification and treatment of endometriosis [6]. MiR-342-3p has been demonstrated to reduce the metabolic gene expression in adipocytes of women with endometriosis [7]. With miR-342 as the miRNA target of this study, our targeting binding prediction further verified Annexin A2 (ANXA2) as the downstream target of miR-342, though it has not been documented. ANXA2, a Ca2+-dependent phospholipid and membrane binding protein, functions as a pivotal player on various

Methods

Discussion

Conclusion