Department of Interventional Radiology, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
Department of Vascular Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, P.R. China.
Mol Med Rep. 2019 Jun;19(6):5195-5202. doi: 10.3892/mmr.2019.10196. Epub 2019 Apr 25.
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.
MicroRNAs (miRNAs) 被认为是肿瘤进展中基因表达的关键调节因子,尽管它们在缺血诱导的血管生成中的作用尚未得到充分描述,包括在外周动脉疾病 (PAD) 中。此外,特定 miRNAs 在 PAD 中的作用机制尚不清楚。逆转录-定量聚合酶链反应分析显示,miR-93 在 PAD 患者和缺氧条件下的 EA.hy926 内皮细胞中显著上调。此外,miR-93 通过增强增殖、迁移和管形成来促进血管生成。细胞周期蛋白依赖性激酶抑制剂 1A (CDKN1A) 被验证为 miR-93 的潜在靶基因,其蛋白和 mRNA 表达水平受到过表达 miR-93 的抑制。此外,通过后肢缺血模型评估 miR-93 在体内血管生成中的作用,结果表明 miR-93 过表达增强了后肢缺血的毛细血管密度和灌注恢复。综上所述,miR-93 有望成为促进血管生成的药理学调节的有前途的靶点,miR-93/CDKN1A 途径可能成为 PAD 的一种新的治疗方法。
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