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载脂蛋白 E 缺陷型小鼠动脉粥样硬化过程中长链非编码 RNA 和信使 RNA 表达变化的系统分析。

Systematic analysis of long non-coding RNA and mRNA expression changes in ApoE-deficient mice during atherosclerosis.

机构信息

Department of Experimental Pharmacology and Toxicology, School of Pharmacy, Jilin University, Changchun, 130021, Jilin, People's Republic of China.

Department of Endocrinology, The First Hospital of Jilin University, Changchun, 130021, Jilin, People's Republic of China.

出版信息

Mol Cell Biochem. 2019 Dec;462(1-2):61-73. doi: 10.1007/s11010-019-03610-y. Epub 2019 Aug 24.

Abstract

Atherosclerosis plays an important role in the pathology of coronary heart disease, cerebrovascular disease, and systemic vascular disease. Long non-coding RNAs (lncRNAs) are involved in most biological processes and are deregulated in many human diseases. However, the expression alteration and precise role of lncRNAs during atherosclerosis are unknown. We report here the systematic profiling of lncRNAs and mRNAs in an ApoE-deficient (ApoE/) mouse model of atherosclerosis. Clariom D solutions for the mouse Affymetrix Gene Chip were employed to analyze the RNAs from control and ApoE/ mice. The functions of the differentially expressed mRNAs and lncRNAs and the relationships of their expression with atherosclerosis were analyzed by gene ontology, co-expression network, pathway enrichment, and lncRNA target pathway network analyses. Quantitative real-time PCR (QRT-PCR) was used to determine the expression of mRNAs and lncRNAs. A total of 2212 differentially expressed lncRNAs were identified in ApoE/ mice, including 1186 up-regulated and 1026 down-regulated lncRNAs (|FC| ≥ 1.1, p < 0.05). A total of 1190 differentially expressed mRNAs were found in the ApoE/ mice with 384 up-regulated and 806 down-regulated (|FC| ≥ 1.1, p < 0.05). Bioinformatics analyses demonstrated extensive co-expression of lncRNAs and mRNAs and concomitant deregulation of multiple signaling pathways associated with the initiation and progression of atherosclerosis. The identified differentially expressed mRNAs and lncRNAs as well as the related signaling pathways may provide systematic information for understanding the pathogenesis and identifying biomarkers for the diagnosis, treatment, and prognosis of atherosclerosis.

摘要

动脉粥样硬化在冠心病、脑血管病和系统性血管疾病的病理学中起着重要作用。长链非编码 RNA(lncRNA)参与大多数生物过程,并在许多人类疾病中失调。然而,lncRNA 在动脉粥样硬化中的表达变化和确切作用尚不清楚。我们在此报告了在载脂蛋白 E 缺陷(ApoE/)小鼠动脉粥样硬化模型中 lncRNA 和 mRNA 的系统分析。Clariom D 解决方案用于分析对照和 ApoE/小鼠的 RNA。通过基因本体、共表达网络、通路富集和 lncRNA 靶通路网络分析,分析差异表达的 mRNA 和 lncRNA 的功能及其与动脉粥样硬化的表达关系。实时定量 PCR(QRT-PCR)用于确定 mRNA 和 lncRNA 的表达。在 ApoE/小鼠中鉴定出 2212 个差异表达的 lncRNA,包括 1186 个上调和 1026 个下调的 lncRNA(|FC|≥1.1,p<0.05)。在 ApoE/小鼠中发现了 1190 个差异表达的 mRNA,其中 384 个上调和 806 个下调(|FC|≥1.1,p<0.05)。生物信息学分析表明,lncRNA 和 mRNA 之间存在广泛的共表达,并且与动脉粥样硬化的发生和进展相关的多个信号通路同时失调。鉴定出的差异表达的 mRNA 和 lncRNA 以及相关的信号通路可能为理解发病机制和鉴定动脉粥样硬化的诊断、治疗和预后的生物标志物提供系统信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2465/6834762/1f88fe1773d5/11010_2019_3610_Fig1_HTML.jpg

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