MicroRNA regulation of molecular pathways as a generic mechanism and as a core disease phenotype.
MicroRNA regulation of molecular pathways as a generic mechanism and as a core disease phenotype.
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DOI：
10.18632/oncotarget.2734
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发表时间：
2015-01-30
期刊：
影响因子：
--
通讯作者：
Efroni S
中科院分区：
文献类型：
--
作者：
Ben-Hamo R;Efroni S
在生物学和生物医学的大多数方面，microRNA作为多种基本细胞过程（如细胞凋亡、分化、增殖和细胞周期）的关键调节剂的作用越来越被认识到。多个microRNA研究的结果在多个通路网络中积累，使我们假设microRNA靶向分子通路。正如我们在这里所展示的，这是一个网络范围内的现象。这项工作使用统计工具显示单个microRNA如何靶向分子通路。我们证明，这种靶向不可能是随机关联的结果，也不可能是microRNA靶点的纯粹计算的结果。此外，关联microRNA途径的最有力证据是证明这些关联与疾病相关的方式。在我们的分析中，我们研究了10种不同类型的癌症，涉及数千个样本，并表明所确定的microRNA通路相关性表明了临床联系和对患者进行分层的能力。这里提出的工作显示了microRNA途径通用调节机制的第一个证据。这种调节与临床表型密切相关。所提出的方法可以通过暴露隐藏的调节机制和临床观察的系统医学观点来催化靶向治疗。
The role of microRNAs as key regulators of a wide variety of fundamental cellular processes, such as apoptosis, differentiation, proliferation and cell cycle is increasingly recognized in most aspects of biology and biomedicine. Accretion of results from multiple microRNA studies over multiple pathway networks, led us to hypothesize that microRNAs target molecular pathways. As we show here, this is a network-wide phenomenon. The work presented, uses statistical tools that show how single microRNAs target molecular pathways. We demonstrate that this targeting could not be the result of random associations and cannot be the result of the sheer numeracy of microRNA targets. Furthermore, the strongest evidence for the association microRNA-pathway, is in a demonstration of the way by which these associations are disease-relevant. In our analyses we study ten different types of cancer involving thousands of samples, and show that the identified microRNA–pathway associations demonstrate a clinical affiliation and an ability to stratify patients. The work presented here shows the first evidence for a mechanism of microRNAs-pathway generic regulation. This regulation is tightly associated with clinical phenotype. The presented approach may catalyze targeted treatment through exposure of hidden regulatory mechanisms and a systems-medicine view of clinical observation.
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3.7
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作者：
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