School of Biological Sciences, The University of Hong Kong, Hong Kong, China.
Bioinformatics. 2018 Sep 15;34(18):3211-3213. doi: 10.1093/bioinformatics/bty320.
MicroRNAs play critical roles in oncogenesis by targeting a few key regulators or a large cohort of genes impinging on downstream signaling pathways. Conversely, miRNA activity is also titrated by competitive endogenous RNA such as lncRNA with sponge effect. Web-based server, miRNACancerMap, aims to unravel lncRNA-miRNA-mRNA tripartite complexity to predict the function and clinical relevance of miRNA with network perspective. In conjunction with large-scale data and information integration, miRNACancerMap implements various algorithms and pipelines to construct dynamic miRNA-centered network with rigorous Systems Biology approaches and the state-of-the-art visualization tool. The capability of the server to generate testable hypotheses was exemplified with cases to identify hub miRNAs regulating most of the differentially-expressed genes involved in cancer stage transition, miRNA-TF pairs shared by pan-cancers and lncRNA sponges validated by multiple datasets. LncRNAs sharing the same miRNAs binding sites as mRNAs can sequester miRNAs and indirectly regulate the activity of the related mRNAs. We have re-annotated traditional microarray chips, and included these datasets in the server to enable validation of the predicted lncRNA-miRNA-mRNA regulations derived from TCGA RNA-seq data. Of note, our server enables identifying miRNAs associated with cancer signaling pathways, and related lncRNA sponges from pan-cancers with only a few mouse clicks.
http://cis.hku.hk/miRNACancerMAP.
Supplementary data are available at Bioinformatics online.
微小 RNA 通过靶向少数关键调节剂或大量影响下游信号通路的基因,在肿瘤发生中发挥关键作用。相反,miRNA 的活性也受到竞争性内源性 RNA(如具有海绵效应的 lncRNA)的调节。基于网络的服务器 miRNACancerMap 旨在揭示 lncRNA-miRNA-mRNA 三方复杂性,以从网络角度预测 miRNA 的功能和临床相关性。该服务器结合了大规模数据和信息集成,通过严格的系统生物学方法和最先进的可视化工具,实施了各种算法和流程,以构建动态 miRNA 为中心的网络。该服务器生成可测试假设的能力通过案例得到了证明,这些案例确定了调节癌症阶段转移中大多数差异表达基因的关键 miRNA、泛癌中共享的 miRNA-TF 对以及通过多个数据集验证的 lncRNA 海绵。与 mRNAs 具有相同 miRNA 结合位点的 lncRNAs 可以隔离 miRNA,并间接调节相关 mRNAs 的活性。我们已经重新注释了传统的微阵列芯片,并将这些数据集包含在服务器中,以验证从 TCGA RNA-seq 数据中预测的 lncRNA-miRNA-mRNA 调控。值得注意的是,我们的服务器能够通过仅点击几下鼠标,从泛癌中识别与癌症信号通路相关的 miRNA 以及相关的 lncRNA 海绵。
http://cis.hku.hk/miRNACancerMAP。
补充数据可在生物信息学在线获得。