A networks method for ranking microRNA dysregulation in cancer.
A networks method for ranking microRNA dysregulation in cancer.
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DOI：
10.1186/1752-0509-7-s5-s3
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发表时间：
2013
影响因子：
--
通讯作者：
Zehner ZE
中科院分区：
文献类型：
--
作者：
Budd WT;Seashols S;Weaver D;Joseph C;Zehner ZE
尽管对它们的确切作用缺乏一致意见，但已知miRNA有助于癌症进展。许多研究利用方法来检测miRNA表达的差异调节。检查所有潜在的失调的miRNA是非常昂贵的，传统上，研究人员将精力集中在最极端失调的miRNA上。这些方法可能忽略了差异表达较少但功能相关性更高的miRNA的贡献。本研究的目的是概述一种方法，不仅利用差异表达，但排名基于其目标的功能相关性的miRNA。这项工作使用基于网络的方法来确定所有实验验证的miRNA靶标的和节点度，以识别前列腺癌发生、进展和转移的潜在调节因子。在这里，我们提出了一种方法，用于识别功能相关的miRNA，有助于前列腺癌的发展。本文表明，miRNA优先调节蛋白质-蛋白质相互作用网络中高度连接的中心蛋白质。在前列腺癌进展过程中差异调节的miRNA的已知靶点在已知参与肿瘤发生的途径中富集。为了证明我们的方法的适用性，我们利用一个独特的前列腺癌进展模型来鉴定可能导致细胞致癌状态的五种miRNA。这些miRNAs中的三种已被其他研究表明在癌症中起作用，但它们在前列腺癌中的确切作用仍不明确。开发方法来确定哪些miRNAs进行生物学和生化分析是重要的，因为传统的方法往往忽略了有助于肿瘤发生的miRNAs。我们的方法应用于前列腺癌进展模型，能够鉴定在前列腺癌发展中起作用的miRNA。
Despite the lack of agreement on their exact roles, it is known that miRNAs contribute to cancer progression. Many studies utilize methods to detect differential regulation of miRNA expression. It is prohibitively expensive to examine all potentially dysregulated miRNAs and traditionally, researchers have focused their efforts on the most extremely dysregulated miRNAs. These methods may overlook the contribution of less differentially expressed but more functionally relevant miRNAs. The purpose of this study was to outline a method that not only utilizes differential expression but ranks miRNAs based on the functional relevance of their targets. This work uses a networks based approach to determine the sum node degree for all experimentally verified miRNA targets to identify potential regulators of prostate cancer initiation, progression and metastasis. Here, we present a method for identifying functionally relevant miRNAs that contribute to prostate cancer development. This paper shows that miRNAs preferentially regulate highly connected, central proteins within a protein-protein interaction network. Known targets of miRNAs differentially regulated during prostate cancer progression are enriched in pathways with known involvement in tumorigenesis. To demonstrate the applicability of our method, we utilized a unique model of prostate cancer progression to identify five miRNAs that may contribute to the oncogenic state of the cell. Three of these miRNAs have been shown by other studies to have a role in cancer but their exact role in prostate cancer remains undefined. Developing methods to determine which miRNAs to carry forward into biological and biochemical analyses is important as traditional approaches often overlook miRNAs that contribute to oncogenesis. Our method applied to a model of prostate cancer progression was able to identify miRNAs with roles in prostate cancer development.