The Potential Regulatory Mechanisms of miR-196a in Huntington's Disease through Bioinformatic Analyses.
The Potential Regulatory Mechanisms of miR-196a in Huntington's Disease through Bioinformatic Analyses.
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DOI：
10.1371/journal.pone.0137637
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Yang SH
中科院分区：
文献类型：
--
作者：
Fu MH;Li CL;Lin HL;Tsai SJ;Lai YY;Chang YF;Cheng PH;Chen CM;Yang SH
高通量筛选是识别疾病进展期间涉及的潜在候选分子的有力工具。然而，分析复杂的数据是从这种方法中获得有用结果的最具挑战性的步骤之一。在此之前，我们在不同的模型中发现了一种特异性的miRNA，miR-196 a，可以改善亨廷顿病（HD）的病理表型，并利用转基因小鼠的纹状体进行了高通量筛选。在这项研究中，我们进一步尝试使用不同的生物信息学工具，包括数据库注释，可视化和集成发现（大卫），分子签名数据库（MSigDB），TargetScan和MetaCore来确定潜在的调控机制。结果表明，miR-196 a主要影响“ABC转运蛋白”、“RIG-I样受体信号通路”、“免疫系统”、“适应性免疫系统”、“组织重构和创伤修复”以及“细胞骨架重构”。此外，miR-196 a还改变了HD的几个明确的途径的表达，如凋亡和细胞粘附。由于这些分析表明调控途径与细胞骨架的修饰高度相关，我们进一步证实了miR-196 a可以促进神经母细胞瘤细胞中的神经突生长，表明miR-196 a可能通过改变细胞骨架结构提供有益的功能。由于在几种神经元疾病中已经报道了细胞骨架的损伤，因此这项研究不仅将提供miR-196 a的潜在工作机制，还将为不同神经元疾病的治疗策略提供见解。
High throughput screening is a powerful tool to identify the potential candidate molecules involved during disease progression. However, analysis of complicated data is one of the most challenging steps on the way to obtaining useful results from this approach. Previously, we showed that a specific miRNA, miR-196a, could ameliorate the pathological phenotypes of Huntington’s disease (HD) in different models, and performed high throughput screening by using the striatum of transgenic mice. In this study, we further tried to identify the potential regulatory mechanisms using different bioinformatic tools, including Database for Annotation, Visualization and Integrated Discovery (DAVID), Molecular Signatures Database (MSigDB), TargetScan and MetaCore. The results showed that miR-196a dominantly altered “ABC transporters”, “RIG-I-like receptor signaling pathway”, immune system”, “adaptive immune system”,“tissue remodeling and wound repair” and “cytoskeleton remodeling”. In addition, miR-196a also changed the expression of several well-defined pathways of HD, such as apoptosis and cell adhesion. Since these analyses showed the regulatory pathways are highly related to the modification of the cytoskeleton, we further confirmed that miR-196a could enhance the neurite outgrowth in neuroblastoma cells, suggesting miR-196a might provide beneficial functions through the alteration of cytoskeleton structures. Since impairment of the cytoskeleton has been reported in several neuronal diseases, this study will provide not only the potential working mechanisms of miR-196a but also insights for therapeutic strategies for use with different neuronal diseases.