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BMC Genomics. 2017 May 30;18(1):418. doi: 10.1186/s12864-017-3790-7.

High-throughput validation of ceRNA regulatory networks.

Author information

1
Texas Children's Cancer Center and Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
2
IBM Research-Zurich, 8803 Rüschlikon, Zurich, Switzerland.
3
Columbia Department of Systems Biology, Center for Computational Biology and Bioinformatics, Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, 10032, USA.
4
Broad Institute, 7 Cambridge Center, Cambridge, MA, 02142, USA.
5
Dana-Farber Cancer Institute, Boston, MA, 02115, USA.
6
Howard Hughes Medical Institute, Chevy Chase, MD, 20815-6789, USA.
7
MOE Key Laboratory of Bioinformatics, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, 100084, China. yangxuerui@tsinghua.edu.cn.
8
Texas Children's Cancer Center and Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA. sumazin@bcm.edu.
9
Columbia Department of Systems Biology, Center for Computational Biology and Bioinformatics, Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, 10032, USA. ac2248@cumc.columbia.edu.
10
Department of Biomedical Informatics, and Department of Biochemistry and Molecular Biophysics, and Institute for Cancer Genetics, Columbia University, New York, USA. ac2248@cumc.columbia.edu.
11
Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, 10032, USA. ac2248@cumc.columbia.edu.

Abstract

BACKGROUND:

MicroRNAs (miRNAs) play multiple roles in tumor biology. Interestingly, reports from multiple groups suggest that miRNA targets may be coupled through competitive stoichiometric sequestration. Specifically, computational models predicted and experimental assays confirmed that miRNA activity is dependent on miRNA target abundance, and consequently, changes in the abundance of some miRNA targets lead to changes to the regulation and abundance of their other targets. The resulting indirect regulatory influence between miRNA targets resembles competition and has been dubbed competitive endogenous RNA (ceRNA). Recent studies have questioned the physiological relevance of ceRNA interactions, our ability to accurately predict these interactions, and the number of genes that are impacted by ceRNA interactions in specific cellular contexts.

RESULTS:

To address these concerns, we reverse engineered ceRNA networks (ceRNETs) in breast and prostate adenocarcinomas using context-specific TCGA profiles, and tested whether ceRNA interactions can predict the effects of RNAi-mediated gene silencing perturbations in PC3 and MCF7 cells._ENREF_22 Our results, based on tests of thousands of inferred ceRNA interactions that are predicted to alter hundreds of cancer genes in each of the two tumor contexts, confirmed statistically significant effects for half of the predicted targets.

CONCLUSIONS:

Our results suggest that the expression of a significant fraction of cancer genes may be regulated by ceRNA interactions in each of the two tumor contexts.

KEYWORDS:

BRCA; LINCS; PRAD; ceRNA; microRNA

PMID:
28558729
PMCID:
PMC5450082
DOI:
10.1186/s12864-017-3790-7
[Indexed for MEDLINE]
Free PMC Article

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