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微小RNA-106b和微小RNA-15b调节心肌梗死中的细胞凋亡和血管生成。

MiR-106b and MiR-15b modulate apoptosis and angiogenesis in myocardial infarction.

作者信息

Liu Zhihua, Yang Dan, Xie Ping, Ren Guomin, Sun Guibo, Zeng Xu, Sun Xiaobo

机构信息

Center for Computational Biology and Bioinformatics, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

出版信息

Cell Physiol Biochem. 2012;29(5-6):851-62. doi: 10.1159/000258197. Epub 2012 May 11.

DOI:10.1159/000258197
PMID:22613985
Abstract

BACKGROUND

MicroRNAs (miRNAs) are identified as crucial gene regulators in response to myocardial infarction (MI). However, the overall relationships between miRNAs and the gene targets which contribute to the cellular phenotypes in MI are not fully elucidated. To make a better understanding towards functional roles of miRNAs in MI, useful information was mined through bioinformatic techniques.

METHOD

MI-related miRNAs were retrieved from publications, and PicTar, TargetScanS, and miRanda programs were used to predict their gene targets. Gene ontology (GO) and pathway analyses of gene targets were applied to uncover functional roles of miRNAs. The miRNA-gene networks were illustrated by Pajek tool. Finally, validation experiments were performed towards two important miRNAs in the networks.

RESULT

Up to 119 MI-related miRNAs were retrieved from publications. GO and pathway analyses for their predicted gene targets demonstrated that these dysregulated miRNAs were enriched in cardiovascular-related phenotypes. Through illustrating miRNA-gene networks, overall relationships between miRNAs and gene targets were detected especially in processes of apoptosis and angiogenesis. Moreover, experimental data supported bioinformatic predictions that miR-106b served as an anti-apoptotic modulator through inhibition of p21 expression and miR-15b displayed anti-angiogenesis activity.

CONCLUSION

The miRNAs played essential roles in pathological processes of MI. Further, miR-106b and miR-15b maybe mediated as robust regulators in apoptosis or angiogenesis following MI, respectively.

摘要

背景

微小RNA(miRNA)被认为是心肌梗死(MI)反应中的关键基因调节因子。然而,miRNA与导致MI细胞表型的基因靶点之间的整体关系尚未完全阐明。为了更好地理解miRNA在MI中的功能作用,通过生物信息学技术挖掘有用信息。

方法

从出版物中检索与MI相关的miRNA,并使用PicTar、TargetScanS和miRanda程序预测其基因靶点。对基因靶点进行基因本体(GO)和通路分析,以揭示miRNA的功能作用。用Pajek工具绘制miRNA-基因网络。最后,对网络中的两个重要miRNA进行验证实验。

结果

从出版物中检索到多达119种与MI相关的miRNA。对其预测基因靶点的GO和通路分析表明,这些失调的miRNA在心血管相关表型中富集。通过绘制miRNA-基因网络,检测到miRNA与基因靶点之间的整体关系,特别是在细胞凋亡和血管生成过程中。此外,实验数据支持生物信息学预测,即miR-106b通过抑制p21表达作为抗凋亡调节剂,而miR-15b显示出抗血管生成活性。

结论

miRNA在MI的病理过程中起重要作用。此外,miR-106b和miR-15b可能分别作为MI后细胞凋亡或血管生成的强大调节因子。

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