MicroRNA/mRNA profiling and regulatory network of intracranial aneurysm.
MicroRNA/mRNA profiling and regulatory network of intracranial aneurysm.
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颅内动脉瘤的 MicroRNA/mRNA 分析和调控网络
DOI：
10.1186/1755-8794-6-36
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发表时间：
2013-09-30
影响因子：
2.7
通讯作者：
Duan R
中科院分区：
文献类型：
--
作者：
Jiang Y;Zhang M;He H;Chen J;Zeng H;Li J;Duan R
研究背景颅内动脉瘤（intracranial aneurysm，IA）是脑血管病中最致命的疾病之一，其特征是血管内皮功能障碍、血管平滑肌细胞表型改变、炎症反应以及由此引起的血管细胞损失和细胞外基质降解。除了环境因素外，遗传学似乎是这种疾病发生的一个非常重要的因素。先前的mRNA表达研究揭示了IA和对照组织之间的大量差异表达基因。然而，微小RNA（miRNA），作为基因表达的转录后调节因子的小的非编码RNA，几乎没有被研究。研究miRNAs可以提供一个假设的机制，潜在的破裂IA。MethodsA微阵列研究进行，以确定差异的microRNA和mRNA之间的患者的IA组织和对照组。定量RT-PCR测定比较两组（14个IA圆顶与14个对照）之间的表达水平用于验证。结果经qPCR检测，在14例IA破裂患者中有18条miRNAs表达下调，包括hsa-mir-133 b、hsa-mir-133 a、hsa-mir-1、hsa-mir-143- 3 p、hsa-mir-145- 3 p、hsa-mir-145- 5 p、hsa-mir-455- 5 p、hsa-mir-143- 5 p、hsa-mir-143- 5 p、h HSA-miR-23 B-3P等，其中11个miRNA是簇：hsa-mir-1/has-mir-133 a、hsa-mir-143/hsa-mir-145、hsa-mir-23 b/hsa-mir-24-1和hsa-mir-29 b-2/hsa-mir-29 c。使用IPA产生了12个预测功能，这些功能与吞噬细胞的迁移、单核白细胞的增殖、单核白细胞的细胞运动、平滑肌细胞的细胞运动等显著相关。结论这些数据支持了可能受miRNA控制的常见疾病机制，并为进一步研究旨在阐明miRNA机制和靶点的IA提供了令人兴奋的方向，从而可能产生新的治疗方法。
BackgroundIntracranial aneurysm (IA) is one of the most lethal forms of cerebrovascular diseases characterized by endothelial dysfunction, vascular smooth muscle cell phenotypic modulation, inflammation and consequently loss of vessel cells and extracellular matrix degradation. Besides environmental factors, genetics seem to be a very important factor in the genesis of this disease. Previous mRNA expression studies revealed a large number of differentially expressed genes between IA and control tissue. However, microRNAs (miRNA), small non-coding RNAs which are post-transcriptional regulators of gene expression, have been barely studied. Studying miRNAs could provide a hypothetical mechanism underlying rupture of IA.MethodsA microarray study was carried out to determine difference in microRNAs and mRNA between patients’ IA tissues and controls. Quantitative RT-PCR assay compared the expression level between two groups (14 IA domes vs. 14 controls) were used for validation. Validated miRNAs were analyzed using Ingenuity Pathway Analysis (IPA) to identify the networks and pathways.Results18 miRNAs were confirmed by qPCR to be robustly down-regulated in 14 ruptured IA patients including hsa-mir-133b, hsa-mir-133a, hsa-mir-1, hsa-mir-143-3p, hsa-mir-145-3p, hsa-mir-145-5p, hsa-mir-455-5p, hsa-mir-143-5p, hsa-mir-23b-3p etc., of which 11 miRNAs are clusters: hsa-mir-1/has-mir-133a, hsa-mir-143/hsa-mir-145, hsa-mir-23b/hsa-mir-24-1, and hsa-mir-29b-2/hsa-mir-29c. 12 predicted functions were generated using IPA which showed significant associations with migration of phagocytes, proliferation of mononuclear leukocytes, cell movement of mononuclear leukocytes, cell movement of smooth muscle cells etc.ConclusionThese data support common disease mechanisms that may be under miRNA control and provide exciting directions for further investigations aimed at elucidating the miRNA mechanisms and targets that may yield new therapies for IA.
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影响因子：
64.8
作者：
Cordes KR;Sheehy NT;White MP;Berry EC;Morton SU;Muth AN;Lee TH;Miano JM;Ivey KN;Srivastava D
通讯作者：
Srivastava D
影响因子：
4.8
作者：
Boucher, Joshua M.;Peterson, Sarah M.;Liaw, Lucy
通讯作者：
Liaw, Lucy
影响因子：
5.3
作者：
Afek, A;Harats, D;George, J
通讯作者：
George, J
影响因子：
2
作者：
Guo, Fuyou;Li, Zhihua;You, Chao
通讯作者：
You, Chao
DOI：
10.1161/atvbaha.110.218149
发表时间：
2011-02
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Chen J;Yin H;Jiang Y;Radhakrishnan SK;Huang ZP;Li J;Shi Z;Kilsdonk EP;Gui Y;Wang DZ;Zheng XL
通讯作者：
Zheng XL