MicroRNA let-7f alleviates vascular endothelial cell dysfunction via targeting HMGA2 under oxygen-glucose deprivation and reoxygenation.

Stroke is a fatal disease with high disability and mortality and there is no credible treatment for stroke at present. Studies on stroke are extensively developed to explore the underlying mechanisms of ischemic and reperfusion injuries. Herein, we investigated the functions of microRNA let-7f (also termed let-7f-5p) in vascular endothelial cell dysfunction. The bEnd.3 cells were stimulated with oxygen-glucose deprivation and reoxygenation (OGD/R) to mimic cell injury in vitro. CCK-8 assays, flow cytometry and western blot analyses were conducted to examine the viability and apoptosis of bEnd.3 cells. Reverse transcription quantitative polymerase chain reaction analyses were employed to measure RNA expression. Endothelial cell permeability in vitro assay was employed to assess endothelial permeability of bEnd.3 cells, and expression levels of proteins associated with cell apoptosis or blood-brain barrier (BBB) were detected by western blot analyses. Luciferase reporter assay was conducted to explore the combination between let-7f and HMGA2. We found that OGD/R induced injuries on endothelial cells (bEnd.3) by decreasing cell viability and promoting cell apoptosis. Let-7f exhibited low expression in bEnd.3 cells under OGD/R. Let-7f overexpression increased the viability of bEnd.3 cells and inhibited cell apoptosis. In addition, the endothelial permeability of bEnd.3 cells was increased by OGD/R and reversed by let-7f overexpression. The levels of tight junction proteins (ZO-1 and occludin) were downregulated by OGD/R and then reversed by let-7f overexpression. Mechanistically, HMGA2 is a target gene of let-7f and its expression was negatively regulated by let-7f. Rescue assays revealed that HMGA2 overexpression reversed the effects of let-7f overexpression on cell viability, cell apoptosis, endothelial permeability, and BBB function. In conclusion, let-7f alleviates vascular endothelial cell dysfunction by downregulating HMGA2 expression under OGD/R.