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冠状动脉粥样硬化患者中差异表达的mRNA及其上游miR-491-5p以及miR-491-5p在血管平滑肌细胞中的功能

Differentially expressed mRNAs and their upstream miR-491-5p in patients with coronary atherosclerosis as well as the function of miR-491-5p in vascular smooth muscle cells.

作者信息

Ding Hui, Pan Quanhua, Qian Long, Hu Chuanxian

机构信息

Department of Cardiovascular Surgery, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huaian, Jiangsu 223300, China.

出版信息

Korean J Physiol Pharmacol. 2022 May 1;26(3):183-193. doi: 10.4196/kjpp.2022.26.3.183.

Abstract

MicroRNAs (miRNAs) regulate gene expression and are biomarkers for coronary atherosclerosis (AS). A novel miRNA-mRNA regulation network of coronary AS still needs to be disclosed. The aim of this study was to analyze potential mRNAs in coronary AS patients and the role of their upstream miR-491-5p in vascular smooth muscle cells (VSMCs). We first confirmed top ten mRNAs according to the analysis from Gene Expression Omnibus database (GSE132651) and examined the expression levels of them in the plaques and serum from AS patients. Five mRNAs (UBE2G2, SLC16A3, POLR2C, PNO1, and AMDHD2) presented significantly abnormal expression in both plaques and serum from AS patients, compared with that in the control groups. Subsequently, they were predicted to be targeted by 11 miRNAs by bioinformatics analysis. Among all the potential upstream miRNAs, only miR-491-5p was abnormally expressed in the plaques and serum from AS patients. Notably, miR-491-5p overexpression inhibited viability and migration, and significantly increased the expression of contractile markers (α-SMA, calponin, SM22α, and smoothelin) in VSMCs. While silencing miR-491-5p promoted viability and migration, and significantly suppressed the expression of α-SMA, calponin, SM22α, and smoothelin. Overall, miR-491-5p targeted UBE2G2, SLC16A3, and PNO1 and regulated the dysfunctions in VSMCs.

摘要

微小RNA(miRNA)可调节基因表达,是冠状动脉粥样硬化(AS)的生物标志物。冠状动脉AS的新型miRNA- mRNA调控网络仍有待揭示。本研究旨在分析冠状动脉AS患者潜在的mRNA及其上游miR-491-5p在血管平滑肌细胞(VSMC)中的作用。我们首先根据基因表达综合数据库(GSE132651)的分析确定了前十个mRNA,并检测了它们在AS患者斑块和血清中的表达水平。与对照组相比,五个mRNA(UBE2G2、SLC16A3、POLR2C、PNO1和AMDHD2)在AS患者的斑块和血清中均呈现出明显异常的表达。随后,通过生物信息学分析预测它们被11个miRNA靶向。在所有潜在的上游miRNA中,只有miR-491-5p在AS患者的斑块和血清中异常表达。值得注意的是,miR-491-5p过表达抑制了VSMC的活力和迁移,并显著增加了收缩标志物(α-SMA、钙调蛋白、SM22α和平滑肌蛋白)的表达。而沉默miR-491-5p则促进了活力和迁移,并显著抑制了α-SMA、钙调蛋白、SM22α和平滑肌蛋白的表达。总体而言,miR-491-5p靶向UBE2G2、SLC16A3和PNO1,并调节VSMC的功能障碍。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cd8/9046892/25b466d94bb3/kjpp-26-3-183-f2.jpg

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