Comprehensive analysis of circRNA expression pattern and circRNA-miRNA-mRNA network in the pathogenesis of atherosclerosis in rabbits.

Comprehensive analysis of circRNA expression pattern and circRNA-miRNA-mRNA network in the pathogenesis of atherosclerosis in rabbits.
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DOI:
10.18632/aging.101541
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发表时间:
2018-09-06
期刊:
Aging
影响因子:
--
通讯作者:
Kong X
Kong X
中科院分区:
其他
文献类型:
--
作者:
Zhang F;Zhang R;Zhang X;Wu Y;Li X;Zhang S;Hou W;Ding Y;Tian J;Sun L;Kong X

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动脉粥样硬化是一种多因素的慢性炎症性疾病,与心脑血管疾病密切相关。circRNA可以作为与mRNA竞争的内源性RNA,并在各种疾病中发挥作用。然而,关于circRNA在动脉粥样硬化中的功能知之甚少。本研究中,病例组中的3只家兔喂饲高脂饲料以诱导动脉粥样硬化,另3只家兔喂饲正常饲料。为了探讨circRNA在动脉粥样硬化中的生物学功能,我们利用RNA-seq技术分析了动脉粥样硬化中circRNA、miRNA和mRNA的表达谱。许多miRNAs、mRNAs和circRNAs在动脉粥样硬化中被鉴定为显著改变。接下来,我们用米兰达工具预测了miRNA-靶标相互作用,并构建了差异表达的circRNA-miRNA-mRNA三元网络。基因本体富集分析表明,网络中的基因参与细胞粘附,细胞活化和免疫反应。此外,我们生成了一个失调的circRNA相关ceRNA网络,并发现七种circRNA(ocu-cirR-novel-18038、-18298、-15993、-17934、-17879、-18036和-14389)与动脉粥样硬化相关。我们发现这些circRNA也在细胞粘附,细胞活化和免疫反应中发挥作用。这些结果表明,circRNA及其竞争mRNA之间的串扰可能在动脉粥样硬化的发展中起着至关重要的作用。
Atherosclerosis is a chronic and multifactorial inflammatory disease and is closely associated with cardiovascular and cerebrovascular diseases. circRNAs can act as competing endogenous RNAs to mRNAs and function in various diseases. However, there is little known about the function of circRNAs in atherosclerosis. In this study, three rabbits in the case group were fed a high-fat diet to induce atherosclerosis and another three rabbits were fed a normal diet. To explore the biological functions of circRNAs in atherosclerosis, we analyzed the circRNA, miRNA and mRNA expression profiles using RNA-seq. Many miRNAs, mRNAs and circRNAs were identified as significantly changed in atherosclerosis. We next predicted miRNA-target interactions with the miRanda tool and constructed a differentially expressed circRNA-miRNA-mRNA triple network. A gene ontology enrichment analysis showed that genes in the network were involved in cell adhesion, cell activation and the immune response. Furthermore, we generated a dysregulated circRNA-related ceRNAs network and found seven circRNAs (ocu-cirR-novel-18038, -18298, -15993, -17934, -17879, -18036 and -14389) were related to atherosclerosis. We found these circRNAs also functioned in cell adhesion, cell activation and the immune response. These results show that the crosstalk between circRNAs and their competing mRNAs might play crucial roles in the development of atherosclerosis.
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