Cargando…

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 net...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5728403/
https://www.ncbi.nlm.nih.gov/pubmed/29156009
http://dx.doi.org/10.1093/nar/gkx1072
_version_ 1783286024085962752
author 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
author_facet 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
author_sort Nikolic, Iva
collection PubMed
description 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.
format Online
Article
Text
id pubmed-5728403
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Oxford University Press
record_format MEDLINE/PubMed
spelling pubmed-57284032017-12-18 Discovering cancer vulnerabilities using high-throughput micro-RNA screening 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 Nucleic Acids Res Data Resources and Analyses 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. Oxford University Press 2017-12-15 2017-11-16 /pmc/articles/PMC5728403/ /pubmed/29156009 http://dx.doi.org/10.1093/nar/gkx1072 Text en © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Data Resources and Analyses
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
Discovering cancer vulnerabilities using high-throughput micro-RNA screening
title Discovering cancer vulnerabilities using high-throughput micro-RNA screening
title_full Discovering cancer vulnerabilities using high-throughput micro-RNA screening
title_fullStr Discovering cancer vulnerabilities using high-throughput micro-RNA screening
title_full_unstemmed Discovering cancer vulnerabilities using high-throughput micro-RNA screening
title_short Discovering cancer vulnerabilities using high-throughput micro-RNA screening
title_sort discovering cancer vulnerabilities using high-throughput micro-rna screening
topic Data Resources and Analyses
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5728403/
https://www.ncbi.nlm.nih.gov/pubmed/29156009
http://dx.doi.org/10.1093/nar/gkx1072
work_keys_str_mv AT nikoliciva discoveringcancervulnerabilitiesusinghighthroughputmicrornascreening
AT elsworthbenjamin discoveringcancervulnerabilitiesusinghighthroughputmicrornascreening
AT dodsoneoin discoveringcancervulnerabilitiesusinghighthroughputmicrornascreening
AT wusunnyz discoveringcancervulnerabilitiesusinghighthroughputmicrornascreening
AT gouldcathrynm discoveringcancervulnerabilitiesusinghighthroughputmicrornascreening
AT mestdaghpieter discoveringcancervulnerabilitiesusinghighthroughputmicrornascreening
AT marshallglennm discoveringcancervulnerabilitiesusinghighthroughputmicrornascreening
AT horvathlisag discoveringcancervulnerabilitiesusinghighthroughputmicrornascreening
AT simpsonkaylenej discoveringcancervulnerabilitiesusinghighthroughputmicrornascreening
AT swarbrickalexander discoveringcancervulnerabilitiesusinghighthroughputmicrornascreening