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

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.

Relationships between Indicators of Lower Extremity Artery Disease and miRNA Expression in Peripheral Blood Mononuclear Cells

“…Elevated expression of miR-124-3p in whole blood samples of patients with PAD was found to be negatively correlated with ABI values and was proposed to be associated with PAD severity [ 38 ]. Similarly, higher serum levels of miR-93 were found to be positively related to the severity of PAD measured by ABI [ 41 ]. Downregulation of miR-126 in plasma was associated with low ABI and the occurrence of symptomatic peripheral artery disease in diabetic patients [ 42 ].…”

“…In previous research, an increase in the expression level of miR-124-3p induced by ischemic conditions was negatively correlated with ABI [ 38 ]. Higher serum levels of miR-93 have previously been found to be positively associated with PAD severity measured by ABI scores [ 41 ]. Downregulation of miR-126 in plasma was associated with lower ABI and the occurrence of symptomatic peripheral artery disease in diabetic patients [ 42 ].…”

Effect of X-rays on transcript expression of rat brain microvascular endothelial cells: role of calcium signaling in X-ray-induced endothelium damage

“…There are very few reports showed the directly evidence that the Prkar2b, Plk4, and Bub3 involved in BMECs damage. However, Cdkn1a-encoded protein plays a key role in proliferation, migration and tube formation in response to hypoxia in endothelial cells [39]. In addition, others demonstrated that CDKN1A protein can inhibit cultured BMECs apoptosis [35].…”

miR-548j-5p regulates angiogenesis in peripheral artery disease

“…Previous studies have shown that specific miRNA expression profiles in patients with PAD may serve as prognostic predictors 7 . In addition, some miRNAs, such as miR-93 8 and miR-let-7 g 9 , have been shown to mediate angiogenesis through various molecular pathways. However, the associations between miRNAs and PAD have not yet been fully characterized.…”