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兔颈动脉粥样硬化中的功能性 lncRNA-miRNA-mRNA 网络。

Functional lncRNA-miRNA-mRNA networks in rabbit carotid atherosclerosis.

机构信息

Department of Ultrasound, The 2nd Affiliated Hospital of Harbin Medical University, Harbin 150081, Heilongjiang, China.

Department of Ultrasound, The First Affiliated Hospital of Xiamen University, Xiamen 361003, Fujian, China.

出版信息

Aging (Albany NY). 2020 Feb 11;12(3):2798-2813. doi: 10.18632/aging.102778.

Abstract

Atherosclerosis is one of the most common clinical cardiovascular disorders. Accumulating evidence indicates that lncRNAs exert critical functions in atherosclerosis; however, their functional roles and regulatory mechanisms remain unclear. In this study, we induced atherosclerotic plaques in three rabbit carotid arteries through an atherogenic diet and balloon injury; three age-matched rabbits were fed normal chow and served as controls. We thoroughly investigated the RNA (mRNA, lncRNA and miRNA) expression profiles in atherosclerotic rabbit carotid models with deep RNA sequencing. We identified several significantly differentially expressed RNAs. The corresponding lncRNA-miRNA-mRNA network was constructed, and the significantly dysregulated network was selected. Furthermore, Gene Ontology and  Kyoto Encyclopedia of Genes and Genomes analyses indicated that the mRNAs in the network were involved in leukocyte activation, cell proliferation, cell adhesion molecules and cytokine-cytokine receptor interaction. After rigorous screening, we obtained a differentially expressed lncRNA-miRNA-mRNA interaction network associated with atherosclerosis. In the network, and upregulate the , , and genes by competitively binding to the miRNA . and upregulate , and genes by competitively binding to the miRNA .

摘要

动脉粥样硬化是最常见的临床心血管疾病之一。越来越多的证据表明,lncRNAs 在动脉粥样硬化中发挥着关键作用;然而,它们的功能作用和调节机制尚不清楚。在这项研究中,我们通过致动脉粥样硬化饮食和球囊损伤诱导了三只兔颈动脉中的动脉粥样硬化斑块;三只年龄匹配的兔子喂食正常饲料作为对照。我们通过深度 RNA 测序全面研究了动脉粥样硬化兔颈动脉模型中的 RNA(mRNA、lncRNA 和 miRNA)表达谱。我们鉴定了几个显著差异表达的 RNA。构建了相应的 lncRNA-miRNA-mRNA 网络,并选择了显著失调的网络。此外,基因本体论和京都基因与基因组百科全书分析表明,网络中的 mRNAs 参与白细胞激活、细胞增殖、细胞黏附分子和细胞因子-细胞因子受体相互作用。经过严格筛选,我们获得了一个与动脉粥样硬化相关的差异表达 lncRNA-miRNA-mRNA 相互作用网络。在网络中,和通过竞争性结合 miRNA 上调、和基因。和通过竞争性结合 miRNA 上调、和基因。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b87c/7041763/62db23c5f261/aging-12-102778-g001.jpg

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