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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增殖、侵袭和迁移。

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

机构信息

Department of Cardiology, Tianjin Nankai Hospital, Tianjin, China (mainland).

Department of Toxicology, Technical Center for Safety of Industrial Products, Tianjin Entry Exit Inspection and Quarantine Bureau, Dongli, Tianjin, China (mainland).

出版信息

Med Sci Monit. 2019 Oct 9;25:7581-7590. doi: 10.12659/MSM.916522.

DOI:10.12659/MSM.916522
PMID:31595884
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6796703/
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.

摘要

背景

研究表明,微小 RNA(miRNAs)在血管平滑肌细胞(VSMCs)的生物学功能中发挥着重要作用。然而,miR-149-5p 在 VSMCs 中的功能和相关分子机制尚不清楚。

材料与方法

我们分别使用 MTT 检测、Transwell 检测和划痕愈合检测来测量转染 miR-149-5p 模拟物或抑制剂的 VSMCs 的增殖、侵袭和迁移。生物信息学工具和荧光素酶报告基因检测用于验证 miR-149-5p 与组蛋白去乙酰化酶 4(HDAC4)之间的关系。采用挽救实验来确认 miR-149-5p 和 HDAC4 在调节 VSMCs 生物学功能中的相互作用。

结果

PDGF-bb 诱导的 VSMCs 中 miR-149-5p 表达下调。研究还发现,miR-149-5p 过表达抑制了 VSMCs 的增殖、侵袭和迁移,而 miR-149-5p 敲低则表现出相反的效果。此外,发现 HDAC4 是 miR-149-5p 的潜在靶标,可挽救 miR-149-5p 介导的 VSMCs 增殖、侵袭和迁移。

结论

我们证实,miR-149-5p 通过调节 HDAC4 抑制 VSMCs 的生物学功能,这可能为 VSMC 生长相关疾病提供一个有效的治疗靶点。

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