Genome-wide microRNA changes in human intracranial aneurysms.
Genome-wide microRNA changes in human intracranial aneurysms.
复制标题
人类颅内动脉瘤的全基因组 microRNA 变化。
DOI：
10.1186/s12883-014-0188-x
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发表时间：
2014-10-10
期刊：
影响因子：
2.6
通讯作者：
Jiang F
中科院分区：
文献类型：
--
作者：
Liu D;Han L;Wu X;Yang X;Zhang Q;Jiang F
颅内动脉瘤是大脑动脉的病理性扩张，而颅内动脉瘤的破裂会导致危及生命的蛛网膜下腔出血。颅内动脉瘤发病的分子机制尚不清楚。MicroRNAs在调节血管生物学和疾病方面起着重要作用。在本研究中，我们对microRNAs的表达进行了全基因组的表征，并结合转录组的变化进行了综合分析。对6例颅内动脉瘤和6例正常颞浅动脉进行了全基因组microRNA筛查。每个病例和对照配对分别与性别、年龄(±5岁)和高血压病史相匹配。使用Agilent Human miRNA阵列进行微阵列分析。与正常动脉相比，我们鉴定了在动脉瘤组织中差异表达的157个microRNA(P <； 0.0 5和折叠变化 ≥ 2)，其中72个上调，85个下调。改变的microRNA包括内皮丰富的microRNAs，如let-7家族成员、miR-17、miR-23b、miR-126、hsa-miR-24-1和miR-222，以及血管平滑肌丰富的miRNAs，如miR-143和miR-145。此外，参与调节血管平滑肌细胞增殖、凋亡和表型转变等功能的miR-1、miR-10a、miR-125b和miR-26a也发生了变化。相比之下，参与单核细胞和巨噬细胞功能的microRNAs，如miR-155、miR-146a、miR-223和miR-124a没有显著变化。生物信息学分析表明，这些改变的microRNAs与几个与动脉瘤形成相关的生物学过程有关，包括炎症、细胞外基质调节失调、平滑肌细胞增殖、程序性细胞死亡和对氧化应激的反应。有趣的是，我们发现潜在的microRNA靶基因的一部分属于蛋白质翻译机制，包括各种真核翻译起始因子和核糖体蛋白，这一发现与我们之前的转录组数据高度相关，转录组数据显示，核糖体蛋白的多个基因以及翻译起始和延伸因子在人类颅内动脉瘤中显著下调。我们的结果支持，失控的microRNAs可能在颅内动脉瘤中起致病作用。蛋白质翻译过程的中断可能在颅内动脉瘤的发展中起致病作用。本文的在线版本(doi：10.1186/s12883-0140188-x)包含补充材料，授权用户可以使用。
Intracranial aneurysms are pathological dilatations of the cerebral artery, while rupture of intracranial aneurysms causes life-threatening subarachnoid hemorrhage. The molecular mechanisms of pathogenesis of intracranial aneurysms are poorly understood. MicroRNAs have fundamental roles in modulating vascular biology and disease. In the present study, we carried out a genome-wide characterization on expressions of microRNAs, and performed integrative analyses in conjunction with changes of the transcriptome in human intracranial aneurysms. Genome-wide microRNA screening was performed in 6 intracranial aneurysmal samples and 6 normal superficial temporal arteries. Each case and control pair was individually matched with gender, age (±5 years), and high blood pressure history. Microarray analysis was performed using Agilent Human miRNA arrays. As compared to normal arteries, we identified 157 microRNAs that were differentially expressed in the aneurysmal tissue (P < 0.05 and fold change ≥ 2), including 72 upregulated and 85 downregulated. The changed microRNAs included endothelium-enriched microRNAs such as members of the let-7 family, miR-17, miR-23b, miR-126, hsa-miR-24-1 and miR-222, and vascular smooth muscle-enriched miRNAs such as miR-143 and miR-145. Moreover, miR-1, miR-10a, miR-125b, and miR-26a, which were implicated in modulating vascular smooth muscle cell functions such as proliferation, apoptosis and shift of phenotype, were also changed. In contrast, microRNAs involved in monocyte and macrophage functions, such as miR-155, miR-146a, miR-223, and miR-124a, were not significantly changed. Bioinformatic analysis revealed that the changed microRNAs were associated with several biological processes related to aneurysm formation, including inflammation, dysregulation of extracellular matrix, smooth muscle cell proliferation, programmed cell death, and response to oxidative stress. Interestingly, we found that a subset of the potential microRNA target genes belonged to the protein translation machinery, including various eukaryotic translation initiation factors and ribosomal proteins, and this finding was highly correlated with our previous transcriptome data showing that multiple genes of the ribosomal proteins and translation initiation and elongation factors were significantly downregulated in human intracranial aneurysms. Our results support that dysregulated microRNAs may have a pathogenic role in intracranial aneurysms. Disruption of the protein translation process may have a pathogenic role in the development of intracranial aneurysms. The online version of this article (doi:10.1186/s12883-014-0188-x) contains supplementary material, which is available to authorized users.
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DOI：
10.1073/pnas.93.16.8750
发表时间：
1996-08-06
影响因子：
11.1
作者：
Hannan, RD;Stefanovsky, V;Rothblum, LI
通讯作者：
Rothblum, LI
影响因子：
3.3
作者：
Caranci, F.;Briganti, F.;Muto, M.
通讯作者：
Muto, M.
影响因子：
8.3
作者：
Aoki, Tomohiro;Kataoka, Hiroharu;Hashimoto, Nobuo
通讯作者：
Hashimoto, Nobuo
颅内动脉瘤的 MicroRNA/mRNA 分析和调控网络
影响因子：
2.7
作者：
Jiang Y;Zhang M;He H;Chen J;Zeng H;Li J;Duan R
通讯作者：
Duan R
DOI：
10.1007/978-1-60761-987-1_18
发表时间：
2011-01-01
期刊：
DATA MINING IN PROTEOMICS: FROM STANDARDS TO APPLICATIONS
影响因子：
--
作者：
Kohl, Michael;Wiese, Sebastian;Warscheid, Bettina
通讯作者：
Warscheid, Bettina