Discovering cancer vulnerabilities using high-throughput micro-RNA screening

Iva Nikolic, Benjamin Elsworth, Eoin Dodson, Sunny Z Wu, Cathryn M Gould, Pieter Mestdagh, Glenn M Marshall, Lisa G Horvath, Kaylene J Simpson, Alexander Swarbrick

Research output: Contribution to journalArticle (Academic Journal)peer-review

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Abstract

Micro-RNAs (miRNAs) are potent regulators of gene expression and cellular phenotype. Each miRNA has the potential to target hundreds of transcripts within the cell thus controlling fundamental cellular processes such as survival and proliferation. Here, we exploit this important feature of miRNA networks to discover vulnerabilities in cancer phenotype, and map miRNA-target relationships across different cancer types. More specifically, we report the results of a functional genomics screen of 1280 miRNA mimics and inhibitors in eight cancer cell lines, and its presentation in a sophisticated interactive data portal. This resource represents the most comprehensive survey of miRNA function in oncology, incorporating breast cancer, prostate cancer and neuroblastoma. A user-friendly web portal couples this experimental data with multiple tools for miRNA target prediction, pathway enrichment analysis and visualization. In addition, the database integrates publicly available gene expression and perturbation data enabling tailored and context-specific analysis of miRNA function in a particular disease. As a proof-of-principle, we use the database and its innovative features to uncover novel determinants of the neuroblastoma malignant phenotype.

Original languageEnglish
Article numbergkx1072
Pages (from-to)12657-12670
Number of pages14
JournalNucleic Acids Research
Volume45
Issue number22
Early online date16 Nov 2017
DOIs
Publication statusPublished - 15 Dec 2017

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