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Exploring regulatory networks of miR-96 in the developing inner ear

Research output: Contribution to journalArticle

Morag A Lewis, Annalisa Buniello, Jennifer M Hilton, Fei Zhu, William I Zhang, Stephanie Evans, Stijn van Dongen, Anton J Enright, Karen P Steel

Original languageEnglish
Article number23363
JournalScientific Reports
Volume6
Early online date18 Mar 2016
DOIs
StateE-pub ahead of print - 18 Mar 2016

Documents

  • Lewis_gold

    srep23363.pdf, 1 MB, application/pdf

    17/05/2016

    Final published version

    CC BY

King's Authors

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.

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