Downregulation of microRNA-451 improves cell migration, invasion and tube formation in hypoxia-treated HUVECs by targeting MIF

Angiogenesis is a critical process of recovery from cerebrovascular disease. A growing body of evidence has confirmed that microRNAs (miRNAs/miRs) have an important role in the modulation of angiogenesis under physiological and pathological conditions including cerebral ischemia injury (CII). Therefore, the aim of the present study was to explore the function and mechanism of microRNAs in regulating angiogenesis using a cell model of CII. Firstly, a miRNA microarray was performed to analyze miRNA expression in serum samples from patients with cerebral ischemia and the results revealed that miR-451 was one of the miRNAs that was the most significantly downregulated. Subsequently, human umbilical vein endothelial cells (HUVECs) were used as an in vitro model to further explore the mechanisms governing angiogenesis during hypoxia. The results demonstrated that overexpression of miR-451 had a significantly anti-angiogenic effect by suppressing tube formation, migration and wound healing in vitro. By contrast, reducing the expression of miR-451 promoted HUVEC migration and tubulogenesis under normoxic conditions. The present study further identified that macrophage migration inhibitory factor (MIF), an important angiogenic regulator, was a novel target of miR-451 that could reverse the effects of miR-451 on the regulation of angiogenesis in HUVECs under hypoxic or normoxic conditions. These results revealed that downregulation of miR-451 promotes angiogenesis by targeting MIF in hypoxic HUVECs and indicated that miR-451 is a potential candidate for CII therapeutics.