A microRNA profile comparison between thoracic aortic dissection and normal thoracic aorta indicates the potential role of microRNAs in contributing to thoracic aortic dissection pathogenesis
A microRNA profile comparison between thoracic aortic dissection and normal thoracic aorta indicates the potential role of microRNAs in contributing to thoracic aortic dissection pathogenesis
复制标题
胸主动脉夹层与正常胸主动脉之间的 microRNA 谱比较表明 microRNA 在胸主动脉夹层发病机制中的潜在作用
DOI：
10.1016/j.jvs.2010.11.113
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发表时间：
2011-05-01
影响因子：
4.3
通讯作者：
Jing, Zaiping
中科院分区：
文献类型：
--
作者：
Liao, Mingfang;Zou, Sili;Jing, Zaiping
目的：我们的目的是通过对胸主动脉夹层（TAD）和正常胸主动脉的miRNA谱进行比较，确定可能在主动脉夹层中起重要作用的重要microRNAs （miRNAs）。方法：采用miRNA芯片分析TAD患者（n = 6）与年龄匹配的无主动脉疾病供体（NA; n = 6）主动脉组织miRNA表达谱的差异。进一步进行定量逆转录聚合酶链反应（qRT-PCR），随着样本数的增加，验证所选择的12个miRNAs的表达情况（TAD n = 12; NA n = 8）。使用计算搜索预测差异表达的mirna的潜在靶标。对预测的靶基因进行生物信息学分析（基因本体、通路和网络分析），为进一步的研究做准备。此外，进行Western blotting以确认生物信息学发现。结果：miRNA微阵列显示TAD组和NA组的miRNA表达差异。在TAD组中，18个mirna表达上调，56个mirna表达下调（倍数变化bbb2， P < 0.01）。qRT-PCR通过微阵列分析验证了七个选定mirna的表达在统计学上是一致的。结合我们之前的蛋白质组学研究，靶基因预测显示一些mirna与其靶蛋白相互表达。靶基因相关通路分析显示，与NA组相比，TAD组的5条通路发生了显著变化，尤其是局灶黏附和丝裂原活化蛋白激酶（MAPK）信号通路。通过进一步进行miRNA基因网络分析，我们发现mir-29和mir-30家族可能分别在这两条通路中发挥调控作用。结论：我们的研究结果表明，TAD主动脉介质中miRNAs表达谱发生了显著变化。这些结果可能为TAD的发病机制提供重要的见解。本研究还提示局灶黏附和MAPK信号通路可能在TAD的发病机制中发挥重要作用。[J] .中华外科杂志，2011;53:1341-9.]
Objectives: Our aim was to identify important microRNAs (miRNAs) that might play an important role in contributing to aortic dissection by conducting a miRNA profile comparison between thoracic aortic dissection (TAD) and normal thoracic aorta.Methods:The differentially expressed miRNA profiles of the aortic tissue between TAD patients (n = 6) and age-matched donors without aortic diseases (NA; n = 6) were analyzed by miRNA microarray. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was further performed to verify the expression of 12 selected miRNAs with an increased number of samples (TAD n = 12; NA n = 8). The potential targets of the differentially expressed miRNAs were predicted using computational searches. Bioinformatic analyses of the predicted target genes (gene ontology, pathway and network analysis) were done for further research. Additionally, Western blotting was performed to confirm the bioinformatics findings.Results: The miRNA microarray revealed differentially expressed miRNAs between the TAD and NA groups. In the TAD group, 18 miRNAs were upregulated and 56 were downregulated (fold change >2, P < .01). qRT-PCR verified statistically consistent expression of seven selected miRNAs with microarray analysis. Combined with our previous proteomics study, target gene prediction revealed that some miRNAs reciprocally expressed with their targeted proteins. Target gene-related pathway analysis showed a significant change in five pathways in the TAD group compared with the NA group, especially the focal adhesion and the mitogen-activated protein kinase (MAPK) signaling pathways. By further conducting miRNA gene network analysis, we found that the mir-29 and mir-30 families are likely to play a role in the regulation of these two pathways, respectively.Conclusions: Our results indicate that miRNAs expression profiles in aortic media from TAD were significantly changed. These results may provide important insights into TAD disease mechanisms. This study also suggests that the focal adhesion and MAPK signaling pathways might play important roles in the pathogenesis of TAD. (J Vasc Surg 2011;53:1341-9.)