The HCMV-encoded miR-UL36-3p promotes angiogenesis of endothelial cells by downregulating FOXO3

Abstract

Background: Human cytomegalovirus (HCMV) infection is related to the acceleration of transplant vascular sclerosis, atherosclerosis, and coronary restenosis. A shared theme of these vascular illnesses is pathologic angiogenesis. Nevertheless, how HCMV infection causes angiogenesis is not fully understood. Human serum contains HCMV-encoded miRNAs, and it is unclear whether these virus-derived miRNAs can regulate angiogenesis. This research looks into HCMV-encoded miRNA's role in angiogenesis of endothelial cells.

Methods: Endothelial cell proliferation was examined by CCK8 assay, and cell migration capability was established using a Transwell Boyden Chamber. Western blotting alongside luciferase reporter assay verified the direct regulation of FOXO3 by HCMV-encoded miRNAs, including hcmv-miR-UL36-3p. hcmv-miR-UL36-3p's pro-angiogenic action was examined by angiogenesis assays (in vivo) and capillary tube formation (in vitro), which were performed by giving C57BL/6J mice subcutaneous Matrigel injections containing bFGF along with simultaneous injections of either hcmv-miR-UL36-3p or ncRNA once every 4 days. After 8 days, Matrigel plugs were examined.

Results: hcmv-miR-UL36-3p was upregulated in patients with atherosclerosis. Overexpression of hcmv-miR-UL36-3p enhanced capillary tube development, motility, and proliferation in endothelial cells. hcmv-miR-UL36-3p promoted endothelial cell tube formation through directly binding to and downregulating FOXO3. Experiments in mice further confirmed that hcmv-miR-UL36-3p promoted angiogenesis in vivo.

Conclusions: The HCMV-encoded miR-UL36-3p can trigger angiogenesis in endothelial cells by targeting FOXO3. Our work provides a conceivable mechanism of how HCMV-encoded miRNAs contribute to vascular illness.

Keywords

angiogenesis / atherosclerosis / endothelial cell / FOXO3 / HCMV / miRNA

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