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功能网络分析揭示人类心脏中的多功能微小RNA。

Functional Network Analysis Reveals Versatile MicroRNAs in Human Heart.

作者信息

Xu Yingqi, Zhu Wenliang, Sun Yong, Wang Zhe, Yuan Wei, Du Zhimin

出版信息

Cell Physiol Biochem. 2015;36(4):1628-43. doi: 10.1159/000430324.

Abstract

BACKGROUND

Acting on many mRNAs allows the power of a single miRNA to modulate multiple pathophysiological phenotypes. One question is whether versatile miRNAs exist in the pathological scenarios of myocardial infarction (MI) and heart failure (HF).

METHODS

A hypergeometric analysis, in combination with network-based functional analyses, was performed on the available human protein interaction and miRNA-gene association data to highlight versatile miRNAs among the significantly dysregulated miRNAs in MI and HF. In vivo, mice models of MI and HF were then established to investigate whether dysregulated expression be undertaken by versatile miRNA identified here.

RESULTS

Systematic analyses really identified the previously validated miRNAs that have been verified of multiple important roles in MI and HF, demonstrating method effectiveness. By using this means, we innovatively revealed the vital role of miR-7 in maintaining the dynamic balance of protein interactions and its obvious overexpression in MI and HF that implies pathological involvement. Functional experiments are definitely needed for further revealing its potential influences on MI- or HF-led myocardial injury.

CONCLUSION

Our results have implications not only for the coming miRNA-based strategy in treating MI and HF but also for further understanding on gene regulation by miRNAs in human heart.

摘要

背景

作用于多种信使核糖核酸(mRNA)使得单个微小核糖核酸(miRNA)能够调节多种病理生理表型。一个问题是,在心肌梗死(MI)和心力衰竭(HF)的病理情况下是否存在多功能的miRNA。

方法

结合基于网络的功能分析,对现有的人类蛋白质相互作用和miRNA-基因关联数据进行超几何分析,以突出MI和HF中显著失调的miRNA中的多功能miRNA。然后在体内建立MI和HF小鼠模型,以研究这里鉴定的多功能miRNA是否会发生表达失调。

结果

系统分析确实鉴定出了先前已验证的在MI和HF中具有多种重要作用的miRNA,证明了该方法的有效性。通过这种方法,我们创新性地揭示了miR-7在维持蛋白质相互作用动态平衡中的重要作用,以及其在MI和HF中的明显过表达,这意味着其参与了病理过程。进一步揭示其对MI或HF所致心肌损伤的潜在影响肯定需要功能实验。

结论

我们的结果不仅对即将到来的基于miRNA的治疗MI和HF的策略有启示,而且对进一步理解miRNA在人类心脏中的基因调控也有启示。

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