Discovering cancer vulnerabilities using high-throughput micro-RNA screening. Issue 22 (16th November 2017)

• Record Type: Journal Article
• Authors: Nikolic, Iva; Elsworth, Benjamin; Dodson, Eoin; Wu, Sunny Z.; Gould, Cathryn M.; Mestdagh, Pieter; Marshall, Glenn M.; Horvath, Lisa G.; Simpson, Kaylene J.; Swarbrick, Alexander
• Is Part Of: Nucleic acids research. Volume 45:Issue 22(2017)
• Page Start: 12657
• Page End: 12670
• Publication Date: 2017-11-16
• Subjects: Nucleic acids -- Periodicals; Molecular biology -- Periodicals; 572.805
• DOI: 10.1093/nar/gkx1072
• Languages: English
• ISSNs: 0305-1048

Abstract

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.