miRNACancerMAP: an integrative web server inferring miRNA regulation network for cancer

Summary 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. Availability and implementation http://cis.hku.hk/miRNACancerMAP. Supplementary information Supplementary data are available at Bioinformatics online.

[1]  D. Bartel,et al.  Predicting effective microRNA target sites in mammalian mRNAs , 2015, eLife.

[2]  Anjali J. Koppal,et al.  Supplementary data: Comprehensive modeling of microRNA targets predicts functional non-conserved and non-canonical sites , 2010 .

[3]  Di Wu,et al.  miRCancer: a microRNA-cancer association database constructed by text mining on literature , 2013, Bioinform..

[4]  Xiaowei Wang,et al.  miRDB: an online resource for microRNA target prediction and functional annotations , 2014, Nucleic Acids Res..

[5]  Jing Li,et al.  dbDEPC 2.0: updated database of differentially expressed proteins in human cancers , 2011, Nucleic Acids Res..

[6]  George A. Calin,et al.  MicroRNAs — the micro steering wheel of tumour metastases , 2009, Nature Reviews Cancer.

[7]  Michael Kertesz,et al.  The role of site accessibility in microRNA target recognition , 2007, Nature Genetics.

[8]  H. Dweep,et al.  miRWalk2.0: a comprehensive atlas of microRNA-target interactions , 2015, Nature Methods.

[9]  Paul Ahlquist,et al.  MicroRNA 29c is down-regulated in nasopharyngeal carcinomas, up-regulating mRNAs encoding extracellular matrix proteins , 2008, Proceedings of the National Academy of Sciences.

[10]  Charles E. Vejnar,et al.  miRmap: Comprehensive prediction of microRNA target repression strength , 2012, Nucleic acids research.

[11]  P. Pandolfi,et al.  A coding-independent function of gene and pseudogene mRNAs regulates tumour biology , 2010, Nature.

[12]  C. Sander,et al.  Analysis of microRNA-target interactions across diverse cancer types , 2013, Nature Structural &Molecular Biology.

[13]  Chi-Ying F. Huang,et al.  miRTarBase: a database curates experimentally validated microRNA–target interactions , 2010, Nucleic Acids Res..

[14]  J. Rinn,et al.  Integrative analyses reveal a long noncoding RNA-mediated sponge regulatory network in prostate cancer , 2016, Nature Communications.

[15]  Yadong Wang,et al.  miR2Disease: a manually curated database for microRNA deregulation in human disease , 2008, Nucleic Acids Res..

[16]  C. Sander,et al.  Integrative genomic profiling of human prostate cancer. , 2010, Cancer cell.

[17]  Hui Zhou,et al.  starBase v2.0: decoding miRNA-ceRNA, miRNA-ncRNA and protein–RNA interaction networks from large-scale CLIP-Seq data , 2013, Nucleic Acids Res..

[18]  Angela M. Liu,et al.  microRNA-122 as a regulator of mitochondrial metabolic gene network in hepatocellular carcinoma , 2010, Molecular systems biology.

[19]  Ting Wang,et al.  OncomiRDB: a database for the experimentally verified oncogenic and tumor-suppressive microRNAs , 2014, Bioinform..