circSnd1 promotes atherosclerosis progression through the miR-485-3p/Olr1 signaling pathway.
circSnd1 promotes atherosclerosis progression through the miR-485-3p/Olr1 signaling pathway.
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DOI：
10.1016/j.heliyon.2023.e17366
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发表时间：
2023-06
期刊：
影响因子：
4
通讯作者：
Fan, Pengcheng
中科院分区：
文献类型：
--
作者：
Yang, Lin;Lin, Yuhao;Wang, Chao;Fan, Pengcheng
环状RNA参与动脉粥样硬化性心血管疾病的发生发展。识别和验证与动脉粥样硬化(AS)相关的关键竞争内源性RNA(CerNA)网络对于了解AS的发展具有重要意义。本研究的目的是研究CircRNA-miRNA-mRNA网络，确定一个关键的CircRNA，并探讨其在动脉粥样硬化发生发展中的作用。AS模型中差异表达的mRNAs(DEM)和CircRNAs(DECs)来自基因表达总表(GEO)数据库中的数据集。用R软件和Cytoscape软件构建CENA网络并进行可视化。通过双荧光素酶报告实验和RNA下拉实验验证了所选择的CERNA轴。使用针对CircRNA、miRNA模拟物、miRNA抑制剂或基因过表达载体的siRNA进行体外功能研究。用ELISA法和Western blotting法检测炎症和脂质转运相关蛋白。此外，还建立了AS小鼠模型，并用重组腺相关病毒载体进行治疗，以进一步验证所选择的CENA轴对AS的发生和/或发展的影响。在25条途径中共富集了497个DEM，并在此基础上选择了CIRC_0082139(CircSnd1)/miR-485-3p/Olr1轴。在体外，证实了该轴上三个分子之间的相互作用，并发现它影响炎症和脂质运输，其特征是炎症因子(IL-6、IL-8、肿瘤坏死因子-α、单核细胞趋化蛋白-1、血管细胞黏附分子-1和ICAM-1)和脂质运输相关基因包括ABCA1、Abcg1、LdlR、HdlBP、LP-PLA2和SREBP-1c的显著变化。通过动物实验，我们进一步证实了CircSnd1/miR-485-3p/Olr1轴调控这些分子，并参与体内AS的形成和/或发展。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。
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. 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 in vitro 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. A total of 497 DEMs were enriched in 25 pathways, based on which the circ_0082139 (circSnd1)/miR-485-3p/Olr1 axis was selected. In vitro, 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 in vivo. The circSnd1/miR-485-3p/Olr1 axis participates in the formation and development of atherosclerosis by regulating inflammation and lipid transport.
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