环状Snd1通过miR-485-3p/Olr1信号通路促进动脉粥样硬化进展。
circSnd1 promotes atherosclerosis progression through the miR-485-3p/Olr1 signaling pathway.
作者信息
Yang Lin, Lin Yuhao, Wang Chao, Fan Pengcheng
机构信息
Vascular Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.
出版信息
Heliyon. 2023 Jun 15;9(6):e17366. doi: 10.1016/j.heliyon.2023.e17366. eCollection 2023 Jun.
BACKGROUND
Circular RNAs (circRNAs) participate in the development of atherosclerotic cardiovascular disease. Identifying and verifying the key competing endogenous RNA (ceRNA) network related to atherosclerosis (AS) is significant for understanding the development of AS. The aim of this study was to investigate the circRNA-miRNA‒mRNA network, identify a key circRNA and explore its role in the development of atherosclerosis.
METHODS
Differentially expressed mRNAs (DEMs) and circRNAs (DECs) in the AS model were obtained from datasets in the Gene Expression Omnibus (GEO) database. R software and Cytoscape software were used to construct and visualize the ceRNA network. The dual-luciferase reporter experiment and the RNA pull-down experiment were used to verify the selected ceRNA axis. siRNA targeting circRNA, miRNA mimic, miRNA inhibitor, or gene overexpression plasmid was used for functional studies. ELISA and western blotting were used to detect inflammation and lipid transport-related proteins. Furthermore, an AS mouse model was established and treated with recombinant adeno-associated viral vectors to further verify the influence of the selected ceRNA axis on the occurrence and/or development of AS.
RESULTS
A total of 497 DEMs were enriched in 25 pathways, based on which the circ_0082139 (circSnd1)/miR-485-3p/Olr1 axis was selected. , the interaction among the three molecules of this axis was validated and it was found to affect inflammation and lipid transport, which were characterized by the significant change of inflammatory factors (Il-6, Il-8, Tnf-α, Mcp-1, Vcam-1, and Icam-1), and lipid transport-related genes, including Abca1, Abcg1, Ldlr, Hdlbp, Lp-pla2, and Srebp-1c. Through animal experiments, we further verified that the circSnd1/miR-485-3p/Olr1 axis regulated these molecules and participated in the formation and/or development of AS .
CONCLUSIONS
The circSnd1/miR-485-3p/Olr1 axis participates in the formation and development of atherosclerosis by regulating inflammation and lipid transport.
背景
环状RNA（circRNAs）参与动脉粥样硬化性心血管疾病的发展。识别和验证与动脉粥样硬化（AS）相关的关键竞争性内源RNA（ceRNA）网络对于理解AS的发展具有重要意义。本研究的目的是研究circRNA-miRNA-mRNA网络，鉴定关键circRNA并探索其在动脉粥样硬化发展中的作用。
方法
从基因表达综合数据库（GEO）的数据集中获取AS模型中差异表达的mRNA（DEMs）和circRNA（DECs）。使用R软件和Cytoscape软件构建并可视化ceRNA网络。采用双荧光素酶报告实验和RNA下拉实验验证所选的ceRNA轴。使用靶向circRNA的siRNA、miRNA模拟物、miRNA抑制剂或基因过表达质粒进行功能研究。采用酶联免疫吸附测定（ELISA）和蛋白质印迹法检测炎症和脂质转运相关蛋白。此外，建立AS小鼠模型并用重组腺相关病毒载体进行处理，以进一步验证所选ceRNA轴对AS发生和/或发展的影响。
结果
共497个DEMs富集于25条通路，据此选择了circ_0082139（circSnd1）/miR-485-3p/Olr1轴。验证了该轴三个分子之间的相互作用，发现其影响炎症和脂质转运，表现为炎症因子（Il-6、Il-8、Tnf-α、Mcp-1、Vcam-1和Icam-1）以及脂质转运相关基因（包括Abca1、Abcg1、Ldlr、Hdlbp、Lp-pla2和Srebp-1c）的显著变化。通过动物实验，我们进一步验证了circSnd1/miR-485-3p/Olr1轴调节这些分子并参与AS的形成和/或发展。
结论
circSnd1/miR-485-3p/Olr1轴通过调节炎症和脂质转运参与动脉粥样硬化的形成和发展。
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