Shen YZ, Yang GP, Ma QM, Wang YS, Wang X. Regulation of lncRNA-ENST on Myc-mediated mitochondrial apoptosis in mesenchymal stem cells: In vitro evidence implicated for acute lung injury therapeutic potential. World J Stem Cells 2025; 17(3): 100079 [DOI: 10.4252/wjsc.v17.i3.100079]
Corresponding Author of This Article
Xin Wang, Medical Center of Burn Plastic and Wound Repair, The First Affiliated Hospital of Nanchang University, No. 17 Yongwai Zhengjie, Donghu District, Nanchang 330006, Jiangxi Province, China. 18772407841@163.com
Research Domain of This Article
Medicine, Research & Experimental
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
World J Stem Cells. Mar 26, 2025; 17(3): 100079 Published online Mar 26, 2025. doi: 10.4252/wjsc.v17.i3.100079
Regulation of lncRNA-ENST on Myc-mediated mitochondrial apoptosis in mesenchymal stem cells: In vitro evidence implicated for acute lung injury therapeutic potential
Ye-Zhou Shen, Guang-Ping Yang, Qi-Min Ma, Yu-Song Wang, Xin Wang
Ye-Zhou Shen, Qi-Min Ma, Yu-Song Wang, Department of Critical Care Medicine, Shanghai East Hospital, Tongji University, Shanghai 200120, China
Guang-Ping Yang, Xin Wang, Medical Center of Burn Plastic and Wound Repair, The First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
Co-first authors: Ye-Zhou Shen and Guang-Ping Yang.
Author contributions: Shen YZ and Yang GY contributed equally to the study design, data analysis, and manuscript preparation and are co-first authors of this manuscript; Shen YZ and Wang X were involved in the study design; Shen YZ and Yang GP mainly conducted the experiments and the statistical analyses, and wrote the manuscript; Ma QM and Wang YS assisted in data analysis. All authors have read the final manuscript and approved the submitted version.
Supported by the Peak Supporting Clinical Discipline of Shanghai Health Bureau, No. 2023ZDFC0104; and the National Key R&D Program of China, No. 2019YFA0110601.
Institutional review board statement: The study described in this manuscript involved the use of stem cell-derived extracellular vesicles (exosomes) in vitro, without the involvement of any human or animal subjects. As such, it did not require ethical review or approval from an Institutional Review Board or Institutional Ethics Committee. The research was conducted in compliance with all relevant guidelines and regulations for in vitro research, and no ethical concerns were raised in the context of this study.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: Technical appendix, statistical code, and dataset available upon reasonable request from the corresponding author at 18772407841@163.com.
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: Xin Wang, Medical Center of Burn Plastic and Wound Repair, The First Affiliated Hospital of Nanchang University, No. 17 Yongwai Zhengjie, Donghu District, Nanchang 330006, Jiangxi Province, China. 18772407841@163.com
Received: August 6, 2024 Revised: December 4, 2024 Accepted: February 5, 2025 Published online: March 26, 2025 Processing time: 226 Days and 17 Hours
Abstract
BACKGROUND
Acute lung injury (ALI) is a fatal and heterogeneous disease. While bone marrow mesenchymal stem cells (BMSCs) have shown promise in ALI repair, their efficacy is compromised by a high apoptotic percentage. Preliminary findings have indicated that long noncoding RNA (lncRNA)-ENST expression is markedly downregulated in MSCs under ischemic and hypoxic conditions, establishing a rationale for in vitro exploration.
AIM
To elucidate the role of lncRNA-ENST00000517482 (lncRNA-ENST) in modulating MSC apoptosis.
METHODS
Founded on ALI in BEAS-2B cells with lipopolysaccharide, this study employed a transwell co-culture system to study BMSC tropism. BMSCs were genetically modified to overexpress or knockdown lncRNA-ENST. After analyzing the effects on autophagy, apoptosis and cell viability, the lncRNA-ENST/miR-539/c-MYC interaction was confirmed by dual-luciferase assays.
RESULTS
These findings have revealed a strong correlation between lncRNA-ENST levels and the apoptotic and autophagic status of BMSCs. On the one hand, the over-expression of lncRNA-ENST, as determined by Cell Counting Kit-8 assays, increased the expression of autophagy markers LC3B, ATG7, and ATG5. On the other hand, it reduced apoptosis and boosted BMSC viability. In co-cultures with BEAS-2B cells, lncRNA-ENST overexpression also improved cell vitality. Additionally, by downregulating miR-539 and upregulating c-MYC, lncRNA-ENST was found to influence mitochondrial membrane potential, enhance BMSC autophagy, mitigate apoptosis and lower the secretion of pro-inflammatory cytokines interleukin-6 and interleukin-1β. Collectively, within the in vitro framework, these results have highlighted the therapeutic potential of BMSCs in ALI and the pivotal regulatory role of lncRNA-ENST in miR-539 and apoptosis in lipopolysaccharide-stimulated BEAS-2B cells.
CONCLUSION
Our in vitro results show that enhanced lncRNA ENST expression can promote BMSC proliferation and viability by modulating the miR-539/c-MYC axis, reduce apoptosis and induce autophagy, which has suggested its therapeutic potential in the treatment of ALI.
Core Tip: In this research, we established an acute lung injury (ALI) model and manipulated long noncoding RNA (lncRNA)-ENST levels in bone marrow mesenchymal stem cells (BMSCs) using a lentiviral system. We discovered that lncRNA-ENST00000517482 is a pivotal regulator of BMSC apoptosis and autophagy in ALI. Modulating lncRNA-ENST00000517482 not only reduces apoptosis and induces autophagy in BMSCs but also enhances their viability, offering a novel approach to enhance ALI treatment efficacy via the miR-539/c-MYC axis.
