MicroRNA-93 regulates angiogenesis in peripheral arterial disease by targeting CDKN1A

MicroRNAs (miRNAs) are considered to be critical mediators of gene expression with respect to tumor progression, although their role in ischemia-induced angiogenesis is poorly characterized, including in peripheral arterial disease (PAD). Furthermore, the underlying mechanism of action of specific miRNAs in PAD remains unknown. Reverse transcription-quantitative polymerase chain reaction analysis revealed that microRNA-93 (miR-93) was significantly upregulated in patients with PAD and in the EA.hy926 endothelial cells in response to hypoxia. Additionally, miRNA (miR)-93 promoted angiogenesis by enhancing proliferation, migration and tube formation. Cyclin dependent kinase inhibitor 1A (CDKN1A), verified as a potential target gene of miR-93, was inhibited by overexpressed miR-93 at the protein and mRNA expression levels. Furthermore, a hind-limb ischemia model served to evaluate the role of miR-93 in angiogenesis in vivo, and the results demonstrated that miR-93 overexpression enhanced capillary density and perfusion recovery from hind-limb ischemia. Taken together, miR-93 was indicated to be a promising target for pharmacological regulation to promote angiogenesis, and the miR-93/CDKN1A pathway may function as a novel therapeutic approach in PAD.