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A densely interconnected genome-wide network of microRNAs and oncogenic pathways revealed using gene expression signatures

 Chia Huey Ooi  ;  Hue Kian Oh  ;  Hannah Zhu’Ai Wang  ;  Angie Lay Keng Tan  ;  Jeanie Wu  ;  Minghui Lee  ;  Sun Young Rha  ;  Hyun Cheol Chung  ;  David Marc Virshup  ;  Patrick Tan 
 PLOS GENETICS, Vol.7(12) : e1002415, 2011 
Journal Title
Issue Date
Carcinogens/metabolism* ; Gene Expression Profiling/methods* ; Gene Expression Regulation, Neoplastic ; Gene Regulatory Networks/genetics* ; Genome, Human ; High-Throughput Screening Assays ; Humans ; MicroRNAs/genetics* ; MicroRNAs/metabolism ; RNA, Messenger/genetics ; Signal Transduction/genetics*
MicroRNAs (miRNAs) are important components of cellular signaling pathways, acting either as pathway regulators or pathway targets. Currently, only a limited number of miRNAs have been functionally linked to specific signaling pathways. Here, we explored if gene expression signatures could be used to represent miRNA activities and integrated with genomic signatures of oncogenic pathway activity to identify connections between miRNAs and oncogenic pathways on a high-throughput, genome-wide scale. Mapping >300 gene expression signatures to >700 primary tumor profiles, we constructed a genome-wide miRNA-pathway network predicting the associations of 276 human miRNAs to 26 oncogenic pathways. The miRNA-pathway network confirmed a host of previously reported miRNA/pathway associations and uncovered several novel associations that were subsequently experimentally validated. Globally, the miRNA-pathway network demonstrates a small-world, but not scale-free, organization characterized by multiple distinct, tightly knit modules each exhibiting a high density of connections. However, unlike genetic or metabolic networks typified by only a few highly connected nodes ("hubs"), most nodes in the miRNA-pathway network are highly connected. Sequence-based computational analysis confirmed that highly-interconnected miRNAs are likely to be regulated by common pathways to target similar sets of downstream genes, suggesting a pervasive and high level of functional redundancy among coexpressed miRNAs. We conclude that gene expression signatures can be used as surrogates of miRNA activity. Our strategy facilitates the task of discovering novel miRNA-pathway connections, since gene expression data for multiple normal and disease conditions are abundantly available
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Rha, Sun Young(라선영) ORCID logo https://orcid.org/0000-0002-2512-4531
Chung, Hyun Cheol(정현철) ORCID logo https://orcid.org/0000-0002-0920-9471
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