Basic Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Apr 26, 2025; 17(4): 100359
Published online Apr 26, 2025. doi: 10.4252/wjsc.v17.i4.100359
Exosomal miR-137-3p targets UBE3C to activate STAT3, promoting migration and differentiation into endometrial epithelial cell of human umbilical cord mesenchymal stem cells under hypoxia
Wan-Yu Zhang, Si-Miao Liu, Han-Bi Wang, Cheng-Yan Deng
Wan-Yu Zhang, Si-Miao Liu, Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
Han-Bi Wang, Cheng-Yan Deng, Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Beijing 100730, China
Co-corresponding authors: Han-Bi Wang and Cheng-Yan Deng.
Author contributions: Deng CY conceptualized and designed the study; Wang HB drafted the initial manuscript; Zhang WY collected the data and carried out the initial analyses; Zhang WY, Liu SM, Wang HB, and Deng CY critically reviewed the manuscript for important intellectual content. Wang HB and Deng CY contributed equally to this manuscript and as co-corresponding authors of this manuscript. All authors approved the final manuscript as submitted and agreed to be accountable for all aspects of the work.
Supported by the National High Level Hospital Clinical Research Funding, No. 2022-PUMCH-B-080 and No. 2022-PUMCH-C-064.
Institutional review board statement: This study didn’t involve human experimentation. The cell lines utilized are commercial in nature and were procured from Cyagen Biosciences, Inc.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The data used to support the findings of this study are available from the corresponding author upon request.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Cheng-Yan Deng, MD, Doctor, Professor, Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, No. 1 Shuaifuyuan, Dongcheng District, Beijing 100730, China. chydmd@hotmail.com
Received: August 14, 2024
Revised: November 29, 2024
Accepted: March 24, 2025
Published online: April 26, 2025
Processing time: 251 Days and 20.8 Hours
Abstract
BACKGROUND

Thin endometrium, leading cause of recurrent implantation failure and infertility, has been found to respond to exosomes.

AIM

To investigate the efficacy of exosomes in addressing the issue of thin endometrium.

METHODS

RNA sequencing and reverse transcription-quantitative polymerase chain reaction were employed to identify differentially expressed microRNAs (miRNAs) in human umbilical cord mesenchymal stem cell (hucMSC) treated with exosomes enriched with endometrial cell-derived components. Additionally, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were conducted to highlight significant enrichment in specific biological pathways, molecular functions, and cellular components. Transwell and wound healing assays were performed to assess migratory potential, and western blotting was detected protein level.

RESULTS

A total of 53 differentially expressed miRNAs were identified in hucMSC treated with exosomes enriched with endometrial cell-derived components, comprising 27 upregulated and 26 downregulated miRNAs, which includes miR-137-3p. Enhanced migratory potential was observed in the Transwell and wound healing assays, and western blotting confirmed the epithelial differentiation of hucMSC and the increased p-signal transducer and activator of transcription 3. These effects were attributed to the upregulation of miR-137-3p.

CONCLUSION

miR-137-3p in exosomes from hypoxia-affected endometrial epithelial cell stimulates the signal transducer and activator of transcription 3 signaling pathway, enhancing the migration and differentiation of hucMSC into endometrial epithelial cell.

Keywords: Endometrial epithelial cells; Exosomes; miR-137-3p; Ubiquitin protein ligase E3C; Signal transducer and activator of transcription 3; Human umbilical cord mesenchymal stem cells

Core Tip: This study uncovers that under hypoxic conditions, exosomal miR-137-3p, by targeting ubiquitin protein ligase E3C, activates signal transducer and activator of transcription 3, thereby enhancing the migration and differentiation of human umbilical cord mesenchymal stem cells (hucMSCs) into endometrial epithelial cells. Through microRNA sequencing and reverse transcription-quantitative polymerase chain reaction validation, it was observed that miR-137-3p is significantly upregulated in hucMSCs when co-cultured with endometrial epithelial cells. Additionally, exosome-based therapeutic system was established to evaluate the role of hucMSCs overexpressing miR-137-3p in therapeutic applications. This discovery offers novel insights into cell therapy under hypoxic environments.