title: Integrated transcriptional and competitive endogenous RNA networks are cross-regulated in permissive molecular environments.
abstract: Competitive endogenous (ce)RNAs cross-regulate each other through sequestration of shared microRNAs and form complex regulatory networks based on their microRNA signature. However, the molecular requirements for ceRNA cross-regulation and the extent of ceRNA networks remain unknown. Here, we present a mathematical mass-action model to determine the optimal conditions for ceRNA activity in silico. This model was validated using phosphatase and tensin homolog (PTEN) and its ceRNA VAMP (vesicle-associated membrane protein)-associated protein A (VAPA) as paradigmatic examples. A computational assessment of the complexity of ceRNA networks revealed that transcription factor and ceRNA networks are intimately intertwined. Notably, we found that ceRNA networks are responsive to transcription factor up-regulation or their aberrant expression in cancer. Thus, given optimal molecular conditions, alterations of one ceRNA can have striking effects on integrated ceRNA and transcriptional networks.
authors.affiliation: Cancer Genetics Program, Department of Medicine and Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Ugo
authors.initials: U
authors.lastname: Ala
authors.forename: Florian A
authors.initials: FA
authors.lastname: Karreth
authors.forename: Carla
authors.initials: C
authors.lastname: Bosia
authors.forename: Andrea
authors.initials: A
authors.lastname: Pagnani
authors.forename: Riccardo
authors.initials: R
authors.lastname: Taulli
authors.forename: Valentine
authors.initials: V
authors.lastname: Léopold
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Tay
authors.forename: Paolo
authors.initials: P
authors.lastname: Provero
authors.forename: Riccardo
authors.initials: R
authors.lastname: Zecchina
authors.forename: Pier Paolo
authors.initials: PP
authors.lastname: Pandolfi
mesh_terms: D002460:Cell Line; D019295:Computational Biology; D018628:Gene Dosage; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D012313:RNA / Q000235:genetics* / Q000378:metabolism; D020218:Response Elements / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D014157:Transcription Factors; D012313:RNA
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