Network analysis of microRNAs, genes and their regulation in human bladder cancer
Network analysis of microRNAs, genes and their regulation in human bladder cancer
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DOI：
10.3892/br.2013.157
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发表时间：
2013-11-01
影响因子：
2.3
通讯作者：
Zhu, Minghui
中科院分区：
文献类型：
--
作者：
Li, Yang;Xu, Zhiwen;Zhu, Minghui
膀胱癌（BC）是世界范围内第五大常见恶性肿瘤，也是癌症相关发病率和死亡率的重要原因。虽然BC是一个严重的健康问题，但关于基因、microRNA（miRNAs）及其宿主基因之间关系的研究一直缺乏。在本研究中，我们评估了来自各种来源的实验验证数据，这些数据报告了miRNA对各种疾病的影响，miRNA靶向mRNA，并将这些数据与miRNA启动子区域内的初始转录因子（TF）结合位点预测相结合。本研究获得的拓扑网络包括差异表达网络、BC相关网络和全局网络。这三个网络可用于评估miRNAs的作用及其在人类BC中的调节。通过比较和分析这三种网络的异同点，确定了最有可能影响特定网络行为的关键节点。结果还显示了潜在的实质性影响的miRNA和TF，其揭示了展示参与机制的子网络以及人类BC中的调节miRNA网络基序。关于差异表达元件（如基因和miRNA）的调节途径证明了自适应关联，包括MYC、TP53、PTEN和10种差异表达的miRNA中的自适应关联和反馈环。差异表达网络部分确定了BC机制。miRNA靶向的人BC基因也在高度相关的通路、细胞周期调控和凋亡中富集。本研究系统阐述了乳腺癌的发病机制，为基因治疗研究者在未来的研究中关注关键基因和miRNAs提供了理论基础。
Bladder cancer (BC) is the fifth most common malignancy occurring worldwide and a significant cause of cancer-related morbidity and mortality. Although BC is a serious health issue, studies available concerning the relationship of genes, microRNAs (miRNAs) and their host genes has been lacking. In the present study, we assessed experimentally validated data from various sources that reported the effect of miRNA on various diseases, miRNA targeting of mRNAs, and combined these data with initial transcription factor (TF) binding site predictions within miRNA promoter regions. Topology networks obtained in this study included the differentially expressed, BC-associated and global networks. The three networks may be used to assess the effect of miRNAs and their regulation in human BC. By comparing and analyzing the similarities and differences among the three networks, key nodes with the largest potential of affecting the behavior of a particular network were identified. The results also showed potentially substantially influential miRNAs and TFs, which revealed subnetworks demonstrating the mechanisms involved as well as regulatory miRNA network motifs in human BC. Regulatory pathways regarding differentially expressed elements, such as genes and miRNAs, demonstrate self-adapting associations including, self-adapting associations and feedback loops in genes MYC, TP53, PTEN and 10 differentially expressed miRNAs. The differentially expressed network partially identified the BC mechanism. miRNA-targeted human BC genes were also enriched in highly relevant pathways, cell cycle regulation and apoptosis. The present study systematically delineated the pathogenesis of BC and provided theoretical foundations for gene therapy investigators to focu attention on key genes and miRNAs in future studies.