Zhou Y, Xu BT, Zhou HY, Shang ZT. Long noncoding ribonucleic acid ENST00000517482 enhances mesenchymal stem cell therapy against acute lung injury. World J Stem Cells 2025; 17(7): 109064 [DOI: 10.4252/wjsc.v17.i7.109064]
Corresponding Author of This Article
Yan Zhou, MD, Department of Respiratory Medicine, Zhuji People’s Hospital, No. 9 Jianmin Road, Taozhu Street, Zhuji 311800, Zhejiang Province, China. 13606850272@163.com
Research Domain of This Article
Respiratory System
Article-Type of This Article
Letter to the Editor
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. Jul 26, 2025; 17(7): 109064 Published online Jul 26, 2025. doi: 10.4252/wjsc.v17.i7.109064
Long noncoding ribonucleic acid ENST00000517482 enhances mesenchymal stem cell therapy against acute lung injury
Yan Zhou, Bo-Tao Xu, Hai-Ying Zhou, Zhong-Tu Shang
Yan Zhou, Hai-Ying Zhou, Zhong-Tu Shang, Department of Respiratory Medicine, Zhuji People’s Hospital, Zhuji 311800, Zhejiang Province, China
Bo-Tao Xu, Department of Cardiothoracic Surgery, Zhuji People’s Hospital, Zhuji 311800, Zhejiang Province, China
Author contributions: Zhou Y contributed to the conceptualization, writing, reviewing and editing; Xu BT and Zhou HY participated in the conceptualization and writing of the original draft; Shang ZT was involved in the formal analysis and validation. All authors participated in drafting the manuscript and all have read and approved the final version of the manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
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: Yan Zhou, MD, Department of Respiratory Medicine, Zhuji People’s Hospital, No. 9 Jianmin Road, Taozhu Street, Zhuji 311800, Zhejiang Province, China. 13606850272@163.com
Received: April 29, 2025 Revised: May 17, 2025 Accepted: July 1, 2025 Published online: July 26, 2025 Processing time: 87 Days and 0.7 Hours
Abstract
Recent findings reveal that long non-coding RNA ENST00000517482 (ENST) protects mesenchymal stem cells (MSCs) from mitochondrial apoptosis via the microRNA-539/c-MYC axis, thereby enhancing their paracrine efficacy against lipopolysaccharide-induced acute lung injury (ALI) in vitro. Furthermore, ENST promotes autophagy through LC3B, autophagy related 7, and autophagy related 5, suggesting a dual role in MSC-mediated lung repair. However, translating these benefits to in vivo applications faces critical challenges. Autophagy, while protective in vitro, may exacerbate epithelial damage during ischemia-reperfusion or hyperoxic ALI if uncontrolled. Additionally, systemic MSC infusion suffers from poor pulmonary engraftment, limiting therapeutic efficiency. To overcome these barriers, future research should prioritize extracellular vehicle-based delivery of ENST-modified MSCs, combined with strategies to fine-tune autophagy via phosphatidylinositol 3-kinase/protein kinase B/mammalian target of the rapamycin or AMP-activated protein kinase/c-Jun-N-terminal kinase modulation. Rigorous validation in endotoxemia and ventilator-induced ALI models, with longitudinal assessment of autophagy and mitochondrial dynamics, will be essential to optimize this approach for clinical translation.
Core Tip: Long non-coding RNA ENST00000517482 enhances the survival of mesenchymal stem cells by protecting mitochondria from apoptosis through the microRNA-539 and c-MYC signaling axis. While this mechanism strengthens stem cell paracrine effects in vitro, its simultaneous activation of autophagy poses potential risks of aggravating lung tissue injury in living organisms. Furthermore, conventional systemic infusion of mesenchymal stem cells results in limited therapeutic efficiency due to poor lung targeting. This article emphasizes the importance of controlling autophagy levels and adopting extracellular vesicle-based delivery systems as critical steps to translate ENST00000517482-mediated stem cell therapies into safe and effective treatments for acute lung injury.
