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胸主动脉瘤中长非编码 RNA 的基因芯片表达谱分析。

Microarray expression profile analysis of long non-coding RNAs in thoracic aortic aneurysm.

机构信息

Department of General Surgery, Beijing Yuho Rehabilitation Hospital of Integrated Chinese and Western Medicine, Beijing, China.

Department of Stomatology, PLA 309th Hospital, Beijing, China.

出版信息

Kaohsiung J Med Sci. 2018 Jan;34(1):34-42. doi: 10.1016/j.kjms.2017.09.005. Epub 2017 Oct 6.

Abstract

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.

摘要

胸主动脉瘤(TAA)是一种高度致命的血管疾病。长链非编码 RNA(lncRNA)是新发现的蛋白质基因调控因子,在心血管生理病理过程中发挥着关键作用。然而,目前只有少数研究关注 TAA 中的 lncRNA。在这项研究中,我们通过第三代 lncRNA 微阵列分析了 TAA(TAA 组,N=6)与正常胸主动脉(对照组,n=6)之间 lncRNA 的差异表达谱。我们发现 1352 个上调和 1624 个下调的 lncRNA 具有差异表达(对数倍数变化>2.0,p<0.01)。通过与细胞外基质(ECM)代谢和血管平滑肌细胞(VSMC)凋亡相关的附近蛋白质编码基因,我们选择了 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 评分,我们鉴定了 8 个候选 lncRNA(4 个上调和 4 个下调),这些 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(HIF1A-AS1、RP11-465L10.10、LOC100506472、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。其中,2 个 lncRNA(RP11-465L10.10 和 CTD-2184D3.5)在主动脉中具有更高的特异性(p<0.01),通过生物信息学进行了分析。进一步的 catRAPID 分析显示,RP11-465L10.10 与髓样锌指基因 1(MZF1)之间存在强烈的 RNA-蛋白质相互作用,MZF1 是 MMP9 的转录因子。然而,在 CTD-2184D3.5 与 MAPK6 的转录因子之间未观察到强烈的 RNA-蛋白质相互作用。总之,我们的研究显示了 TAA 中 lncRNA 的差异表达谱,并揭示了某些 lncRNA 与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新的见解。

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