Li Meiling, Liu Qing, Lei Jiayan, Wang Xiaoliang, Chen Xiaoyun, Ding Yanhui
Department of Clinical Research Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
Department of Clinical Research Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
Biochem Biophys Res Commun. 2017 Nov 4;493(1):270-276. doi: 10.1016/j.bbrc.2017.09.031. Epub 2017 Sep 8.
Atherosclerosis is a progressive condition of the large arteries that can cause coronary artery disease (CAD). Growing amounts of evidence have indicated that microRNAs (miRNAs, miRs) can be used as diagnostic biomarkers in many cellular processes associated with CAD. MiR-362-3p has been implicated in many biological cellular functions. However, little is known about the role of miR-362-3p during atherosclerosis. In the present study, significant downregulation of miR-362-3p was observed in 110 atherosclerotic CAD patients and not in the 84 controls. The upregulation of miR-362-3p was demonstrated to inhibit vascular smooth muscle cell (VSMC) proliferation and migration, and impede the G1/S cell cycle transition. Bioinformatics analysis indicated that a disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1) was a direct target of miR-362-3p. Subsequent experiments demonstrated that miR-362-3p binds to the 3'-untranslated region (UTR) of ADAMTS1 and decreases its levels of mRNA and protein expression. Overexpression of ADAMTS1 partially restored the miR-362-3p-mediated inhibition of VSMC proliferation, cell cycle, and migration. Upregulation of ADAMTS1 in plasma samples was detected in atherosclerotic CAD patients. Taken together, our findings suggested that miR-362-3p inhibits the proliferation and migration of VSMCs by directly targeting ADAMTS1, which might provide novel insight into the molecular mechanisms underlying the action of miR-362-3p in atherosclerosis.
动脉粥样硬化是一种发生于大动脉的进行性疾病，可导致冠状动脉疾病（CAD）。越来越多的证据表明，微小RNA（miRNA，miR）可作为与CAD相关的许多细胞过程中的诊断生物标志物。MiR-362-3p参与了许多生物学细胞功能。然而，关于miR-362-3p在动脉粥样硬化过程中的作用知之甚少。在本研究中，在110例动脉粥样硬化CAD患者中观察到miR-362-3p显著下调，而在84例对照中未观察到。miR-362-3p的上调被证明可抑制血管平滑肌细胞（VSMC）的增殖和迁移，并阻碍G1/S细胞周期转换。生物信息学分析表明，含血小板反应蛋白基序的解聚素和金属蛋白酶1（ADAMTS1）是miR-362-3p的直接靶点。随后的实验表明，miR-362-3p与ADAMTS1的3'-非翻译区（UTR）结合，并降低其mRNA和蛋白表达水平。ADAMTS1的过表达部分恢复了miR-362-3p介导的对VSMC增殖、细胞周期和迁移的抑制作用。在动脉粥样硬化CAD患者的血浆样本中检测到ADAMTS1上调。综上所述，我们的研究结果表明，miR-362-3p通过直接靶向ADAMTS1抑制VSMC的增殖和迁移，这可能为miR-362-3p在动脉粥样硬化中作用的分子机制提供新的见解。
