MicroRNA‑15b participates in the development of peripheral arterial disease by modulating the growth of vascular smooth muscle cells

Abstract

As an atherosclerotic disease, the process of peripheral arterial disease (PAD) is complicated and includes the abnormal proliferation of vascular smooth muscle. The current study aimed to determine the role of microRNA-15b (miR-15b) in the development of PAD and its associated mechanisms. Human vascular smooth muscle cells (hVSMCs) were used in the current study. To assess the effects of miR-15b on hVSMCs, miR-15b was up- or downregulated in hVSMCs using miR-15b mimics or miR-15b inhibitors respectively. Cell viability, migration and apoptosis were then determined via MTT, transwell and flow cytometry assays, respectively. TargetScan bioinformatics software was utilized to predict the targets of miR-15b, and the binding sites between insulin growth factor 1 receptor (IGF1R) and miR-15b were confirmed by dual-luciferase reporter assay. The results reveled that the miR-15b mimic significantly reduced hVSMC cell viability and migration, and promoted cell apoptosis. However, the opposite effect was observed following miR-15b inhibitor transfection. It was also determined that miR-15b directly targeted IGF1R and negatively regulated its expression in hVSMCs. Additionally, the results demonstrated that the miR-15b mimic inhibited the PI3K/AKT signaling pathway in hVSMCs, whereas the miR-15b inhibitor promoted it. Furthermore, the results indicated that the effect of the miR-15b mimic on hVSMCs was reversed by IGF1R overexpression. In conclusion, the data indicated that miR-15b participated in the occurrence and development of PAD by modulating hVSMC proliferation, apoptosis and migration via the regulation of IGF1R expression.

MicroRNA Sequencing Analysis in Obstructive Sleep Apnea and Depression: Anti-Oxidant and MAOA-Inhibiting Effects of miR-15b-5p and miR-92b-3p through Targeting PTGS1-NF-κB-SP1 Signaling

“…In the current study, miR-15b-5p and miR-92b-3p were down-regulated both in the two independent cohorts of OSA patients and in response to IHR stimuli in vitro, and able to counteract oxidative stress-related cell apoptosis. In line with our findings, miR-15b has been shown to inhibit angiogenesis in proliferative diabetic retinopathy via targeting VEGFA, inhibit vascular smooth muscle cells in peripheral artery disease via targeting IGF1R, counteract senescence-associated mitochondrial dysfunction in skin aging via targeting SIRT4, and suppress Th17 Differentiation in multiple sclerosis by targeting O-GlcNAc [ 42 , 43 , 44 , 45 ]. In contrast, miR-15b has been found to augment cell apoptosis in Parkinson’s disease via targeting the GSK-3β/β-catenin signaling pathway, contribute to depression-like behavior in mice by affecting synaptic protein levels and function in the nucleus accumbens, deteriorate cardiomyocyte apoptosis in myocardial infarction via targeting Bcl-2/MAPK3, and contribute to extra-cellular matrix degradation in intervertebral disc degeneration via targeting SMAD3 [ 46 , 47 , 48 , 49 ].…”

“…OSA is independently associated with impaired endothelial function and atherosclerosis through inflammation, oxidative stress, autonomic nervous system activation, and platelet activation [ 40 , 41 ]. Specifically, up-regulations of the miR146b, miR-421, miR-10a, miR-106a, miR-18a, miR-374b, miR-223, and miR-335 genes are implicated in the progression of atherosclerosis, cancer, oxidative stress, ischemic stroke, or insulin resistance, while down-regulations of the miR-150, miR-29c, miR-133a, and miR-145 genes are implicated in protection from heart failure, cancer, or insulin resistance [ 6 , 42 , 43 ].…”

hsa‑miR‑15b‑5p regulates the proliferation and apoptosis of human vascular smooth muscle cells by targeting the ACSS2/PTGS2 axis

“…The present study confirmed this hypothesis, demonstrating that miR-15b mimics significantly reduced the viability and facilitated the apoptosis of human VSMCs, and that opposite effects were observed following miR-15b inhibitor transfection. Further confirmation of this hypothesis was reported in a recent study by Sun et al ( 24 ).…”

“…The known downstream target genes of miR-15b-5p include axin 2( 21 ), progestin and adipoQ receptor family member 3( 22 ), heparanase 2( 23 ), and reversion inducing cysteine rich protein with kazal motifs ( 25 ) in cancer cells, and the insulin like growth factor 1 receptor ( 24 ) in human VSMCs. The present study, for the first time, demonstrated that ACSS2 may also be a direct target of miR-15b-5p using the dual-luciferase reporter system.…”

miR‑15b, a diagnostic biomarker and therapeutic target, inhibits oesophageal cancer progression by regulating the PI3K/AKT signalling pathway

“…miR-15b overexpression alleviated ovarian cancer by inhibiting the PI3K/AKT signalling pathway (43). By contrast, miR-15b participates in the development of peripheral arterial disease by inactivating the PI3K/AKT signalling pathway (44). Therefore, it was speculated that the effects of miR-15b in EC may be related to the PI3K/AKT signalling pathway.…”