miR-149-5p Inhibits Vascular Smooth Muscle Cells Proliferation, Invasion, and Migration by Targeting Histone Deacetylase 4 (HDAC4)

miR-149-5p通过靶向组蛋白去乙酰化酶4(HDAC4)抑制血管平滑肌细胞的增殖、侵袭和迁移

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Abstract

BACKGROUND Studies have demonstrated that microRNAs (miRNAs) have essential roles in biological functions of vascular smooth muscle cells (VSMCs). However, the function and related molecular mechanism of miR-149-5p in VSMCs remains unclear. MATERIAL AND METHODS We used MTT assay, Transwell assay, and wound-healing assay to measure the proliferation, invasion, and migration of VSMCs transfected with miR-149-5p mimics or inhibitors, respectively. Bioinformatics tools and luciferase assay were used to validate the relationship between miR-149-5p and histone deacetylase 4 (HDAC4). Rescue experiments were used to confirm the interaction of miR-149-5p and HDAC4 in regulating biological functions in VSMCs. RESULTS miR-149-5p was downregulated in PDGF-bb-induced VSMCs. It was also found that miR-149-5p overexpression suppressed proliferation, invasion, and migration of VSMCs, while miR-149-5p knockdown showed the opposite effects. Furthermore, HDAC4 was found to be a potential target of miR-149-5p, which rescued miR-149-5p-mediated proliferation, invasion, and migration in VSMCs. CONCLUSIONS We demonstrated that miR-149-5p can suppress biological functions of VSMCs by regulating HDAC4, which might provide a potent therapeutic target for VSMC growth-related diseases.

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