miR-18a-5p Promotes Proliferation and Migration of Vascular Smooth Muscle Cells by Activating the AKT/Extracellular Regulated Protein Kinases (ERK) Signaling Pathway.

BACKGROUND microRNAs (miRNAs) play important roles in abnormal proliferation and migration of vascular smooth muscle cells (VSMCs), which lead to restenosis in coronary artery disease. Nevertheless, the role of miR-18a-5p and how it works in VSMCs remain unknown. MATERIAL AND METHODS miR-18a-5p expression was determined by fluorescence quantitative real-time polymerase chain reaction (qRT-PCR) analysis of tissues from 20 patients with stent restenosis, and rats with carotid artery injury, as well as VSMCs. A cell viability assay was used to measure cell proliferation. Cell migration abilities were assessed by transwell migration assay and wound healing assays. To identify miR-18a-5p targets, a dual-luciferase reporter assay was performed. Western blot analysis and immunofluorescence techniques were used to assess the protein expression levels of AKT and ERK. The rescue effects of miR-18a-5p on the proliferation or migration of VSMCs were evaluated after exposure to the AKT inhibitor MK-2206 and ERK inhibitor PD98059. RESULTS The expression level of miR-18a-5p was significantly higher in the blood serum of patients with stent restenosis and in rats with carotid artery injury, and the expression of AKT and ERK was higher after carotid artery injury. The proliferation and migration abilities of VSMCs were accelerated by the overexpression of miR-18a-5p. It was found that miR-18a-5p directly modulates AKT/ERK signaling. Upregulated miR-18a-5p increased the protein expression levels of AKT and ERK and we found a positive correlation between miR-18a-5p expression level and expression of AKT and ERK. Additionally, the promoting effect of miR-18a-5p on VSMCs proliferation, migration, and invasion was reversed by ERK inhibitor or AKT inhibitor. CONCLUSIONS miR-18a-5p can promote proliferation of VSMCs by activating the AKT/ERK signaling pathway.

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