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

Published version
Peer-reviewed

Type

Article

Change log

Authors

Lewis, Morag A 
Buniello, Annalisa 
Hilton, Jennifer M 
Zhu, Fei 
Zhang, William I 

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.

Description

Keywords

3' Untranslated Regions, Animals, Animals, Newborn, Deafness, Ear, Inner, Gene Expression Profiling, Gene Expression Regulation, Gene Regulatory Networks, Mice, MicroRNAs, Mutation, Oligonucleotide Array Sequence Analysis

Journal Title

Sci Rep

Conference Name

Journal ISSN

2045-2322
2045-2322

Volume Title

6

Publisher

Springer Science and Business Media LLC