Microarray expression profile analysis of long non-coding RNAs in thoracic aortic aneurysm
Microarray expression profile analysis of long non-coding RNAs in thoracic aortic aneurysm
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DOI：
10.1016/j.kjms.2017.09.005
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发表时间：
2018-01-01
影响因子：
3.3
通讯作者：
Yang, Nan
中科院分区：
文献类型：
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作者：
Li, Yang;Yang, Nan
胸主动脉瘤（TAA）是一种高致死性血管疾病。长链非编码RNA（longnoncodingRNAs，lncRNA）是近年来发现的一类重要的蛋白质基因调控因子，在心血管疾病的生理病理过程中发挥着重要作用。然而，有一些研究关注TAA中的lncRNA。本研究应用第三代lncRNA微阵列技术，对TAA（TAA组，N = 6）和正常胸主动脉（对照组，n = 6）的lncRNA表达差异进行分析。我们鉴定了1352个上调和1624个下调的lncRNA的差异表达（对数倍数变化> 2.0，p < 0.01）。通过筛选与细胞外基质（ECM）代谢和血管平滑肌细胞（VSMC）凋亡相关的蛋白编码基因，筛选出12个上调和9个下调的lncRNA进行进一步分析。通过计算碱基的phastCons得分，我们鉴定了8个候选lncRNA（4个上调和4个下调），这些候选lncRNA在物种间具有高度保守性。通过组织特异性分析，我们发现5个lncRNA（HIF 1A-AS 1，RP 11 -465L10.10，LOC 100506472，CTD-2184D3.5和RP-399O19.5）在主动脉组织中高表达，提示它们可能与TAA密切相关。对其中2个主动脉特异性较高（p < 0.01）的lncRNA（RP 11 -465L10.10和CTD-2184D3.5）进行生物信息学分析。进一步的catRAPID分析揭示了RP 11 -465L10.10和髓样锌指基因1（MZF 1）（MMP 9的转录因子）之间的强RNA-蛋白质相互作用。然而，在CTD-2184D3.5和MAPK 6的转录因子之间没有观察到强烈的RNA-蛋白质相互作用。总之，我们的研究显示了不同的lncRNA在TAA的表达谱，并揭示了某些lncRNA和编码基因之间的相互作用。这些数据为TAA的新生物标志物和治疗靶点提供了见解。版权所有（C）2017，高雄医学大学.出版社：Elsevier Taiwan LLC
Thoracic aortic aneurysm (TAA) is a highly lethal vascular disease. Long non-coding RNAs (lncRNAs) are newly discovered as a regulator of protein genes and play critical roles in cardiovascular physio-pathological processes. However, there were a few studies looking at lncRNAs in TAA. In this study, we profiled differential expression of lncRNAs between TAA (TAA group, N = 6) and normal thoracic aorta (control group, n = 6) by third-generation lncRNA microarray. We identified 1352 up-regulated and 1624 down-regulated lncRNAs with differential expression (log fold-change > 2.0, p < 0.01). Through nearby protein-coding gene associated with extracellular matrix (ECM) metabolism and vascular smooth muscle cell (VSMC) apoptosis, 12 up-regulated and 9 down-regulated lncRNAs were selected for further analysis. By calculating phastCons score of base, we identified 8 candidate lncRNAs (4 up-regulated and 4 down-regulated) with high conservation across species. By tissue specificity analysis, we found that 5 lncRNAs (HIF1A-AS1, RP11-465L10.10, LOC100506472, CTD-2184D3.5 and RP-399O19.5) were highly expressed in aortic tissues, suggested that they may be closely associated with TAA. Among them, 2 lncRNAs (RP11-465L10.10 and CTD-2184D3.5) with higher specificity in aorta (p < 0.01) were analyzed by bioinformatics. Further catRAPID analysis revealed a strong RNA-protein interaction between RP11-465L10.10 and myeloid zinc finger gene 1 (MZF1), a transcription factor of MMP9. However, no intense RNA-protein interactions were observed between CTD-2184D3.5 and transcript factors of MAPK6. In conclusions, our study showed differential expression profiles of lncRNAs in TAA and revealed the interaction between certain lncRNAs and coding genes. These data provides insights into new biomarker and therapeutic targets for TAA. Copyright (C) 2017, Kaohsiung Medical University. Published by Elsevier Taiwan LLC.