Regulation of lncRNA-ENST on Myc-mediated mitochondrial apoptosis in mesenchymal stem cells:In vitro evidence implicated for acute lung injury therapeutic potential  

作　　者：Ye-Zhou Shen Guang-Ping Yang Qi-Min Ma Yu-Song Wang Xin Wang 

机构地区：[1]Department of Critical Care Medicine,Shanghai East Hospital,Tongji University,Shanghai 200120,China [2]Medical Center of Burn Plastic and Wound Repair,The First Affiliated Hospital of Nanchang University,Nanchang 330006,Jiangxi Province,China

出　　处：《World Journal of Stem Cells》2025年第3期65-80,共16页世界干细胞杂志(英文)

基　　金：Supported by the Peak Supporting Clinical Discipline of Shanghai Health Bureau,No.2023ZDFC0104;the National Key R&D Program of China,No.2019YFA0110601.

摘　　要：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 overexpression 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 proinflammatory 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 potenti

关 键 词：Long noncoding RNA Mesenchymal stem cell MITOCHONDRIAL Apoptosis AUTOPHAGY Acute lung injury 

分 类 号：R73[医药卫生—肿瘤]