Microarray profiling analysis and validation of novel long noncoding RNAs and mRNAs as potential biomarkers and their functions in atherosclerosis

Microarray profiling analysis and validation of novel long noncoding RNAs and mRNAs as potential biomarkers and their functions in atherosclerosis
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新型长非编码 RNA 和 mRNA 作为潜在生物标志物的微阵列分析和验证及其在动脉粥样硬化中的功能

DOI:
10.1152/physiolgenomics.00077.2019
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发表时间:
2019-12-01
影响因子:
4.6
通讯作者:
Hu, Yan-Wei
Hu, Yan-Wei
中科院分区:
生物学3区
文献类型:
--
作者:
Bai, Huan-Lan;Lu, Zhi-Feng;Hu, Yan-Wei

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长链非编码RNA参与了动脉粥样硬化的发生和发展。然而,lncRNA在动脉粥样硬化中的表达和作用机制仍不清楚。我们应用基因芯片技术检测了人类晚期动脉粥样硬化斑块和正常动脉内膜中lncRNA和mRNA的表达谱。应用基因本体功能富集和通路分析技术,探讨动脉粥样硬化发病机制中的潜在功能和通路。共选择236个lncRNA和488个mRNA用于进一步的损伤途径分析。此外,大多数选择的lncRNA和mRNA的定量RT-PCR测试与高倍数变化的微阵列数据一致。我们还通过ELISA检测了所选基因的相应蛋白水平,结果显示血清SPP 1、CD 36、ATP 6V 0 D2、CHI 3L 1水平与对照组相比显著降低。MYH 11和BDNF在冠心病患者和健康人中的表达存在差异。这些蛋白质与心血管疾病诊断中的一些生化指标相关。此外,受试者操作特征分析显示出良好的诊断性能。微阵列分析和验证差异表达的lncRNA和mRNA在动脉粥样硬化不仅提供了新的见解,这种疾病的发病机制,但也可能揭示新的生物标志物,其诊断和治疗。
Long noncoding (lnc)RNAs have been implicated in the development and progression of atherosclerosis. However, the expression and mechanism of action of lncRNAs in atherosclerosis are still unclear. We implemented microarray analysis in human advanced atherosclerotic plaques and normal arterial intimae to detect the lncRNA and mRNA expression profile. Gene Ontology functional enrichment and pathway analyses were applied to explore the potential functions and pathways involved in the pathogenesis of atherosclerosis. A total of 236 lncRNAs and 488 mRNAs were selected for further Ingenuity Pathway Analysis. Moreover, quantitative RT-PCR tests of most selected lncRNAs and mRNAs with high fold changes were consistent with the microarray data. We also performed ELISA to investigate the corresponding proteins levels of selected genes and showed that serum levels of SPP1, CD36, ATP6V0D2, CHI3L1. MYH11, and BDNF were differentially expressed in patients with coronary heart disease compared with healthy subjects. These proteins correlated with some biochemical parameters used in the diagnosis of cardiovascular diseases. Furthermore, receiver operating characteristic analysis showed a favorable diagnostic performance. The microarray profiling analysis and validation of differentially-expressed lncRNAs and mRNAs in atherosclerosis not only provide new insights into the pathogenesis of this disease but may also reveal new biomarkers for its diagnosis and treatment.