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

MicroRNA-93 通过靶向 CDKN1A 来调节外周动脉疾病的血管生成

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作者:Xiaojun Shu, Youjun Mao, Zhengfei Li, Wenhui Wang, Yaowen Chang, Shengye Liu, Xiao-Qiang Li

Abstract

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.

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