LncRNA HIF1A-AS3 Promotes Glycolysis and Regulates Metabolic Reprogramming in Human Mesenchymal Stem Cells.

Abstract

Introduction: Mesenchymal stem cells (MSCs) play a significant role in shaping and regulating microenvironments. The factors influencing the glycolytic metabolic reprogramming of MSCs remain unknown.

Methods: MSCs were isolated from human umbilical cords and identified using flow cytometry. Glycolysis-related gene expression, glucose consumption, and ATP and lactate production were measured in MSCs with HIF1A-AS3 overexpression or knockdown. The roles of HIF1A-AS3 in the glycolytic pathway and its downstream network were revealed by high-throughput sequencing.

Results: HIF1A-AS3 enhanced the glycolytic level of MSCs by increasing glucose consumption, lactate production, ATP levels, and expression of key glycolytic enzymes (GLUT1, HK2, and PKM2). The downstream signaling pathway of HIF1A-AS3 might be associated with glycosylationrelated diseases.

Discussion: It was demonstrated that HIF1A-AS3, a hypoxia-induced long non‑coding RNA, acted as a critical regulator of glycolytic reprogramming in MSCs. Additionally, HIF1A-AS3 upregulated a distinct subset of interferon‑stimulated genes, suggesting a potential link between metabolic reprogramming and immunomodulation in MSCs. Further mechanistic studies are warranted to elucidate how HIF1A-AS3 regulates these processes.

Conclusion: The study reveals that HIF1A-AS3 is a regulator of the metabolic reprogramming of glycolysis in MSCs. These findings provide new insights into understanding the metabolic regulatory mechanism of MSCs.