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Discovering cancer vulnerabilities using high-throughput micro-RNA screening


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.

Type Journal
ISBN 1362-4962 (Electronic) 0305-1048 (Linking)
Authors Nikolic, I.; Elsworth, B.; Dodson, E.; Wu, S. Z.; Gould, C. M.; Mestdagh, P.; Marshall, G. M.; Horvath, L. G.; Simpson, K. J.; Swarbrick, A.
Responsible Garvan Author Prof Alexander Swarbrick
Published Date 2017-12-15
Published Volume 45
Published Issue 22
Published Pages 12657-12670
Status Published in-print
DOI 10.1093/nar/gkx1072
URL link to publisher's version
OpenAccess link to author's accepted manuscript version