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

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 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 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 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.