Department of Tuina, Binzhou Municipal Hospital of Traditional Chinese Medicine, Binzhou, 256600, Shandong, China.
Department of Supply Room, Affiliated Hospital of Weifang Medical University, Weifang, 261000, Shandong, China.
Mol Biotechnol. 2021 Jul;63(7):595-604. doi: 10.1007/s12033-021-00323-w. Epub 2021 Apr 2.
Atherosclerosis (AS) is a serious healthy burden worldwide, it occurs accompany with the disfunction of vascular smooth muscle cells (VSMCs). MicroRNAs play pivotal role in the pathogenesis of various diseases. This study aimed to investigate the expression and clinical value of miR-199a-3p in patients with asymptomatic AS, and further explore its regulatory role on VSMCs biological function. Quantitative real-time PCR was used to estimate the expression of miR-199a-3p. Correlation of miR-199a-3p with carotid intima-media thickness (CIMT) and C-reactive protein (CRP) was evaluated by Pearson correlation coefficient. A receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic value of miR-199a-3p. Effects of miR-199a-3p on cell proliferation and migration in VSMCs were analyzed using cell-counting method and Transwell assay. Luciferase reporter assay was performed for the target gene analysis. Serum expression of miR-199a-3p was decreased in asymptomatic AS patients compared with the healthy controls. The negative correlations of miR-199a-3p with CIMT and CRP were obtained. The decreased miR-199a-3p was proved to have diagnostic accuracy with an area under the ROC curve (AUC) of 0.912, and was an independent predictor for the occurrence of asymptomatic AS. In VSMCs, overexpression of miR-199a-3p led to inhibited cell proliferation and migration, while the knockdown of miR-199a-3p resulted in the opposite results. SP1 was proved to be the target gene of miR-199a-3p. Taken together, downregulated expression of miR-199a-3p is a candidate diagnostic biomarker in the patients with asymptomatic AS. Overexpression of miR-199a-3p exists suppressive effects on VSMC proliferation and migration, indicating that miR-199a-3p may be a potential therapeutic target for AS treatment.
动脉粥样硬化（AS）是一种严重的全球健康负担，它伴随着血管平滑肌细胞（VSMCs）的功能障碍而发生。microRNAs 在各种疾病的发病机制中发挥着关键作用。本研究旨在探讨无症状 AS 患者中 miR-199a-3p 的表达及其临床价值，并进一步探讨其对 VSMCs 生物学功能的调节作用。采用实时定量 PCR 估计 miR-199a-3p 的表达。通过 Pearson 相关系数评估 miR-199a-3p 与颈动脉内膜中层厚度（CIMT）和 C-反应蛋白（CRP）的相关性。绘制受试者工作特征（ROC）曲线评估 miR-199a-3p 的诊断价值。采用细胞计数法和 Transwell 试验分析 miR-199a-3p 对 VSMCs 增殖和迁移的影响。采用荧光素酶报告基因检测分析靶基因。与健康对照组相比，无症状 AS 患者血清中 miR-199a-3p 的表达降低。miR-199a-3p 与 CIMT 和 CRP 呈负相关。ROC 曲线下面积（AUC）为 0.912，表明降低的 miR-199a-3p 具有诊断准确性，是无症状 AS 发生的独立预测因子。在 VSMCs 中，miR-199a-3p 的过表达导致细胞增殖和迁移受到抑制，而 miR-199a-3p 的敲低则导致相反的结果。SP1 被证明是 miR-199a-3p 的靶基因。综上所述，下调 miR-199a-3p 的表达是无症状 AS 患者的候选诊断生物标志物。miR-199a-3p 的过表达对 VSMC 增殖和迁移具有抑制作用，表明 miR-199a-3p 可能是 AS 治疗的潜在治疗靶点。
