High-throughput validation of ceRNA regulatory networks
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 miR...
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| Format: | Article |
| Language: | English |
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BMC
2017-05-01
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| Series: | BMC Genomics |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12864-017-3790-7 |
| _version_ | 1818967110182764544 |
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| author | Hua-Sheng Chiu María Rodríguez Martínez Mukesh Bansal Aravind Subramanian Todd R. Golub Xuerui Yang Pavel Sumazin Andrea Califano |
| author_facet | Hua-Sheng Chiu María Rodríguez Martínez Mukesh Bansal Aravind Subramanian Todd R. Golub Xuerui Yang Pavel Sumazin Andrea Califano |
| author_sort | Hua-Sheng Chiu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T13:43:35Z |
| format | Article |
| id | doaj.art-c4bf66224d274206a50e8eccb2b548ba |
| institution | Directory Open Access Journal |
| issn | 1471-2164 |
| language | English |
| last_indexed | 2024-12-20T13:43:35Z |
| publishDate | 2017-05-01 |
| publisher | BMC |
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| series | BMC Genomics |
| spelling | doaj.art-c4bf66224d274206a50e8eccb2b548ba2022-12-21T19:38:45ZengBMCBMC Genomics1471-21642017-05-0118111110.1186/s12864-017-3790-7High-throughput validation of ceRNA regulatory networksHua-Sheng Chiu0María Rodríguez Martínez1Mukesh Bansal2Aravind Subramanian3Todd R. Golub4Xuerui Yang5Pavel Sumazin6Andrea Califano7Texas Children’s Cancer Center and Department of Pediatrics, Baylor College of MedicineIBM Research—ZurichColumbia Department of Systems Biology, Center for Computational Biology and Bioinformatics, Herbert Irving Comprehensive Cancer Center, Columbia UniversityBroad InstituteBroad InstituteMOE Key Laboratory of Bioinformatics, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua UniversityTexas Children’s Cancer Center and Department of Pediatrics, Baylor College of MedicineColumbia Department of Systems Biology, Center for Computational Biology and Bioinformatics, Herbert Irving Comprehensive Cancer Center, Columbia UniversityAbstract 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.http://link.springer.com/article/10.1186/s12864-017-3790-7ceRNAmicroRNALINCSPRADBRCA |
| spellingShingle | Hua-Sheng Chiu María Rodríguez Martínez Mukesh Bansal Aravind Subramanian Todd R. Golub Xuerui Yang Pavel Sumazin Andrea Califano High-throughput validation of ceRNA regulatory networks BMC Genomics ceRNA microRNA LINCS PRAD BRCA |
| title | High-throughput validation of ceRNA regulatory networks |
| title_full | High-throughput validation of ceRNA regulatory networks |
| title_fullStr | High-throughput validation of ceRNA regulatory networks |
| title_full_unstemmed | High-throughput validation of ceRNA regulatory networks |
| title_short | High-throughput validation of ceRNA regulatory networks |
| title_sort | high throughput validation of cerna regulatory networks |
| topic | ceRNA microRNA LINCS PRAD BRCA |
| url | http://link.springer.com/article/10.1186/s12864-017-3790-7 |
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