The Number Of Titrated Microrna Species Dictates Cerna Regulation

microRNAs (miRNAs) play key roles in cancer, but their propensity to couple their targets as competing endogenous RNAs (ceRNAs) has only recently emerged. Multiple models have studied ceRNA regulation, but these models did not account for the effects of co-regulation by miRNAs with many targets. We...

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Autores: Chiu, Hua-Sheng, Rodríguez Martínez, María, Komissarova, Elena V., Llobet-Navas, David, Bansal, Mukesh, Paull, Evan O., Silva, José, Yang, Xuerui, Sumazin, Pavel, Califano, Andrea
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2018
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/123906
Acceso en línea:https://hdl.handle.net/2445/123906
Access Level:acceso abierto
Palabra clave:Càncer
Micro RNAs
MicroRNAs
Cancer
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spelling The Number Of Titrated Microrna Species Dictates Cerna RegulationChiu, Hua-ShengRodríguez Martínez, MaríaKomissarova, Elena V.Llobet-Navas, DavidBansal, MukeshPaull, Evan O.Silva, JoséYang, XueruiSumazin, PavelCalifano, AndreaCàncerMicro RNAsMicroRNAsCancermicroRNAs (miRNAs) play key roles in cancer, but their propensity to couple their targets as competing endogenous RNAs (ceRNAs) has only recently emerged. Multiple models have studied ceRNA regulation, but these models did not account for the effects of co-regulation by miRNAs with many targets. We modeled ceRNA and simulated its effects using established parameters for miRNA/mRNA interaction kinetics while accounting for co-regulation by multiple miRNAs with many targets. Our simulations suggested that co-regulation by many miRNA species is more likely to produce physiologically relevant context-independent couplings. To test this, we studied the overlap of inferred ceRNA networks from four tumor contexts-our proposed pan-cancer ceRNA interactome (PCI). PCI was composed of interactions between genes that were coregulated by nearly three-times as many miRNAs as other inferred ceRNA interactions. Evidence from expression-profiling datasets suggested that PCI interactions are predictive of gene expression in 12 independent tumor-and non-tumor contexts. Biochemical assays confirmed ceRNA couplings for two PCI subnetworks, including oncogenes CCND1, HIF1A and HMGA2, and tumor suppressors PTEN, RB1 and TP53. Our results suggest that PCI is enriched for context-independent interactions that are coupled by many miRNA species and are more likely to be context independent.Oxford Univ Press2018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/123906Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1093/nar/gky286Nucleic Acids Research, 2018, Vol. 46, Issue 9, P. 4354-4369https://doi.org/10.1093/nar/gky286cc by-nc (c) Chiu, Hua-Sheng et al., 2018http://creativecommons.org/licenses/by-nc/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1239062026-05-27T06:46:51Z
dc.title.none.fl_str_mv The Number Of Titrated Microrna Species Dictates Cerna Regulation
title The Number Of Titrated Microrna Species Dictates Cerna Regulation
spellingShingle The Number Of Titrated Microrna Species Dictates Cerna Regulation
Chiu, Hua-Sheng
Càncer
Micro RNAs
MicroRNAs
Cancer
title_short The Number Of Titrated Microrna Species Dictates Cerna Regulation
title_full The Number Of Titrated Microrna Species Dictates Cerna Regulation
title_fullStr The Number Of Titrated Microrna Species Dictates Cerna Regulation
title_full_unstemmed The Number Of Titrated Microrna Species Dictates Cerna Regulation
title_sort The Number Of Titrated Microrna Species Dictates Cerna Regulation
dc.creator.none.fl_str_mv Chiu, Hua-Sheng
Rodríguez Martínez, María
Komissarova, Elena V.
Llobet-Navas, David
Bansal, Mukesh
Paull, Evan O.
Silva, José
Yang, Xuerui
Sumazin, Pavel
Califano, Andrea
author Chiu, Hua-Sheng
author_facet Chiu, Hua-Sheng
Rodríguez Martínez, María
Komissarova, Elena V.
Llobet-Navas, David
Bansal, Mukesh
Paull, Evan O.
Silva, José
Yang, Xuerui
Sumazin, Pavel
Califano, Andrea
author_role author
author2 Rodríguez Martínez, María
Komissarova, Elena V.
Llobet-Navas, David
Bansal, Mukesh
Paull, Evan O.
Silva, José
Yang, Xuerui
Sumazin, Pavel
Califano, Andrea
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Càncer
Micro RNAs
MicroRNAs
Cancer
topic Càncer
Micro RNAs
MicroRNAs
Cancer
description microRNAs (miRNAs) play key roles in cancer, but their propensity to couple their targets as competing endogenous RNAs (ceRNAs) has only recently emerged. Multiple models have studied ceRNA regulation, but these models did not account for the effects of co-regulation by miRNAs with many targets. We modeled ceRNA and simulated its effects using established parameters for miRNA/mRNA interaction kinetics while accounting for co-regulation by multiple miRNAs with many targets. Our simulations suggested that co-regulation by many miRNA species is more likely to produce physiologically relevant context-independent couplings. To test this, we studied the overlap of inferred ceRNA networks from four tumor contexts-our proposed pan-cancer ceRNA interactome (PCI). PCI was composed of interactions between genes that were coregulated by nearly three-times as many miRNAs as other inferred ceRNA interactions. Evidence from expression-profiling datasets suggested that PCI interactions are predictive of gene expression in 12 independent tumor-and non-tumor contexts. Biochemical assays confirmed ceRNA couplings for two PCI subnetworks, including oncogenes CCND1, HIF1A and HMGA2, and tumor suppressors PTEN, RB1 and TP53. Our results suggest that PCI is enriched for context-independent interactions that are coupled by many miRNA species and are more likely to be context independent.
publishDate 2018
dc.date.none.fl_str_mv 2018
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/123906
url https://hdl.handle.net/2445/123906
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1093/nar/gky286
Nucleic Acids Research, 2018, Vol. 46, Issue 9, P. 4354-4369
https://doi.org/10.1093/nar/gky286
dc.rights.none.fl_str_mv cc by-nc (c) Chiu, Hua-Sheng et al., 2018
http://creativecommons.org/licenses/by-nc/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by-nc (c) Chiu, Hua-Sheng et al., 2018
http://creativecommons.org/licenses/by-nc/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Oxford Univ Press
publisher.none.fl_str_mv Oxford Univ Press
dc.source.none.fl_str_mv Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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