title: Exploring regulatory networks of miR-96 in the developing inner ear.
abstract: Mutations in the microRNA Mir96 cause deafness in mice and humans. In the diminuendo mouse, which carries a single base pair change in the seed region of miR-96, the sensory hair cells crucial for hearing fail to develop fully and retain immature characteristics, suggesting that miR-96 is important for coordinating hair cell maturation. Our previous transcriptional analyses show that many genes are misregulated in the diminuendo inner ear and we report here further misregulated genes. We have chosen three complementary approaches to explore potential networks controlled by miR-96 using these transcriptional data. Firstly, we used regulatory interactions manually curated from the literature to construct a regulatory network incorporating our transcriptional data. Secondly, we built a protein-protein interaction network using the InnateDB database. Thirdly, gene set enrichment analysis was used to identify gene sets in which the misregulated genes are enriched. We have identified several candidates for mediating some of the expression changes caused by the diminuendo mutation, including Fos, Myc, Trp53 and Nr3c1, and confirmed our prediction that Fos is downregulated in diminuendo homozygotes. Understanding the pathways regulated by miR-96 could lead to potential therapeutic targets for treating hearing loss due to perturbation of any component of the network.
authors.affiliation: Wolfson Centre for Age-Related Diseases, King's College London, Guy's Campus, London SE1 1UL, UK.|Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK.
authors.forename: Morag A
authors.initials: MA
authors.lastname: Lewis
authors.affiliation: Wolfson Centre for Age-Related Diseases, King's College London, Guy's Campus, London SE1 1UL, UK.|Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Buniello
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Hilton
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK.
authors.forename: Fei
authors.initials: F
authors.lastname: Zhu
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK.
authors.forename: William I
authors.initials: WI
authors.lastname: Zhang
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Evans
authors.affiliation: EMBL EBI, Hinxton, Cambridge CB10 1SD.
authors.forename: Stijn
authors.initials: S
authors.lastname: van Dongen
authors.affiliation: EMBL EBI, Hinxton, Cambridge CB10 1SD.
authors.forename: Anton J
authors.initials: AJ
authors.lastname: Enright
authors.affiliation: Wolfson Centre for Age-Related Diseases, King's College London, Guy's Campus, London SE1 1UL, UK.|Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK.
authors.forename: Karen P
authors.initials: KP
authors.lastname: Steel
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D000831:Animals, Newborn; D003638:Deafness / Q000235:genetics* / Q000662:veterinary; D007758:Ear, Inner / Q000254:growth & development*; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; C541554:Mirn96 microRNA, mouse