Human Umbilical Cord Mesenchymal Stem Cell-Derived Extracellular Vesicles Inhibit Endometrial Cancer Cell Proliferation and Migration through Delivery of Exogenous miR-302a.

Xin Li,Kai Wang,Hao Ai,Ju Lei Yao,Li Li Liu

doi:10.1155/2019/8108576

Abstract

MicroRNAs (miRNAs) are potential therapeutic targets in endometrial cancer, but the difficulties associated with their delivery to tumor target cells have hampered their applications. Human umbilical cord mesenchymal stem cells (hUCMSCs) have a well-recognized tumor-homing ability, emphasizing the capacity of tumor-targeted delivery of extracellular vesicles. hUCMSCs release extracellular vesicles rich in miRNAs, which play a vital role in intercellular communication. The purpose of this study was to verify a potential tumor suppressor microRNA, miR-302a, and engineered hUCMSC extracellular vesicles enriched with miR-302a for therapy of endometrial cancer. Here, we observed that miR-302a was significantly downregulated in endometrial cancer tissues when compared with adjacent tissues. Overexpression of miR-302a in endometrial cancer cells robustly suppressed cell proliferation and migration. Meanwhile, the proliferation and migration were significantly inhibited in endometrial cancer cells when cultured with miR-302a-loaded extracellular vesicles derived from hUCMSCs. Importantly, our data showed that engineered extracellular vesicles rich in miR-302 significantly inhibited the expression of cyclin D1 and suppressed AKT signaling pathway in endometrial cancer cells. These results suggested that exogenous miR-302a delivered by hUCMSC-derived extracellular vesicles has exciting potential as an effective anticancer therapy.

Highlights

Endometrial cancer (EC) is the most common gynecologic malignancy, and the incidence of EC has increased markedly with a higher prevalence in younger women [1]
We investigated the role of miR-302a and miR-302a-enriched Extracellular vesicles (EVs) derived from Human umbilical cord mesenchymal stem cells (hUCMSCs) in EC cell proliferation and migration and the underlying mechanisms
The results showed that miR-302a in hUCMSCs was remarkably overexpressed after infection with lentivirus (Figure 4(a))

Summary

Introduction

Endometrial cancer (EC) is the most common gynecologic malignancy, and the incidence of EC has increased markedly with a higher prevalence in younger women [1]. Increase in the incidence of EC and the lack of powerful yet nontoxic treatment strategies indicate the need of developing novel treatment strategies for this malignancy [2]. MiR-302a is located on chromosomal region 4 which acts as a tumor suppressor in different cancer types, such as human melanoma [7], breast cancer [8], malignant germ cell tumor [9], and cervical carcinoma [10]. MiR-302a is located on chromosomal region 4 which acts as a tumor suppressor in different cancer types, such as human melanoma [7], breast cancer [8], malignant germ cell tumor [9], and cervical carcinoma [10]. miR-302a has been reported to reduce cell

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Conclusion