MicroRNA-92 regulates vascular smooth muscle cell function by targeting KLF4 during vascular restenosis and injury

MicroRNAs (miRNAs) contribute to multiple cellular processes in embryonic development and disorders. Several miRNAs are strongly associated with the progression of peripheral vascular disease. Recently, it was reported that miRNA (miR)-92 is one of the most upregulated miRNAs in vascular injury after intervention in the lower extremities; however, the function of miR-92 during proliferative vascular diseases remains unclear and the potential targets of miR-92 are poorly characterized. In this study, we investigated the expression of miR-92 in vitro and in vivo, and explored the associated underlying mechanism. qRT-PCR analysis showed that miR-92 expression was highly upregulated in patients with artery restenosis compared to those without restenosis. Platelet-derived growth factor (PDGF)-BB is regarded as a critical regulator of the phenotypic switch of VSMCs. miR-92 expression was significantly upregulated in PDGF-BB-stimulated VSMCs. Introducing an miR-92 mimic into VSMCs enhanced cell proliferation and migration, and induced S-phase arrest. The luciferase reporter assay revealed that KLF4 is a downstream target gene of miR-92. In vivo, miR-92 overexpression promoted neointimal formation, and thus resulted in a dramatic increase in intimal-medial area and thickness. These results reveal that miR-92 regulates VSMC function by directly targeting KLF4, which may be an important finding useful for the diagnosis and treatment of vascular restenosis and injury, arteriosclerosis, and other proliferative vascular diseases.