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首页> 外文期刊>BMC Medical Genomics >MicroRNA/mRNA profiling and regulatory network of intracranial aneurysm
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MicroRNA/mRNA profiling and regulatory network of intracranial aneurysm

机译：颅内动脉瘤的MicroRNA / mRNA分析和调控网络

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Background Intracranial 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. Methods A 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. Results 18 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. Conclusion These 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.
机译：背景技术颅内动脉瘤（IA）是脑血管疾病的最致命形式之一，其特征在于内皮功能障碍，血管平滑肌细胞表型调节，炎症，进而导致血管细胞丢失和细胞外基质降解。除环境因素外，遗传因素似乎是该疾病发生的重要因素。先前的mRNA表达研究揭示了IA和对照组织之间大量差异表达的基因。然而，很少研究微小RNA（miRNA），即小的非编码RNA，它们是基因表达的转录后调节因子。研究miRNAs可能提供潜在的IA破裂的机制。方法进行了一项微阵列研究，以确定患者IA组织和对照组之间microRNA和mRNA的差异。定量RT-PCR分析比较了两组之间的表达水平（14个IA穹顶对比14个对照）用于验证。使用Ingenuity Pathway Analysis（IPA）分析经过验证的miRNA，以识别网络和途径。结果通过qPCR证实了18例miRNA在14例破裂的IA患者中被强烈下调，包括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等，其中11个miRNA是簇：hsa-mir-1 / has-mir-133a，hsa-mir-143 / hsa-mir-145，hsa-mir-23b / hsa-mir-24-1和hsa-mir-29b-2 / hsa-mir-29c。使用IPA生成的12种预测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密切相关。结论这些数据支持可能在miRNA控制下的常见疾病机制，并提供旨在阐明可能产生IA新疗法的miRNA机制和靶标的进一步研究的令人兴奋的方向。

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