Exploring regulatory networks of miR-96 in the developing inner ear.
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Authors
Lewis, Morag A
Buniello, Annalisa
Hilton, Jennifer M
Zhu, Fei
Zhang, William I
Evans, Stephanie
van Dongen, Stijn
Steel, Karen P
Publication Date
2016-03-18Journal Title
Sci Rep
ISSN
2045-2322
Publisher
Springer Science and Business Media LLC
Volume
6
Pages
23363
Language
eng
Type
Article
This Version
VoR
Physical Medium
Electronic
Metadata
Show full item recordCitation
Lewis, M. A., Buniello, A., Hilton, J. M., Zhu, F., Zhang, W. I., Evans, S., van Dongen, S., et al. (2016). Exploring regulatory networks of miR-96 in the developing inner ear.. Sci Rep, 6 23363. https://doi.org/10.1038/srep23363
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.
Keywords
Animals, Animals, Newborn, Mice, Deafness, MicroRNAs, 3' Untranslated Regions, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Gene Expression Regulation, Mutation, Ear, Inner, Gene Regulatory Networks
Identifiers
External DOI: https://doi.org/10.1038/srep23363
This record's URL: https://www.repository.cam.ac.uk/handle/1810/270960
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