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The miR-183/Taok1 Target Pair Is Implicated in Cochlear Responses to Acoustic Trauma

Acoustic trauma, one of the leading causes of sensorineural hearing loss, induces sensory hair cell damage in the cochlea. Identifying the molecular mechanisms involved in regulating sensory hair cell death is critical towards developing effective treatments for preventing hair cell damage. Recently...

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Autores principales: Patel, Minal, Cai, Qunfeng, Ding, Dalian, Salvi, Richard, Hu, Zihua, Hu, Bo Hua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3589350/
https://www.ncbi.nlm.nih.gov/pubmed/23472202
http://dx.doi.org/10.1371/journal.pone.0058471
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author Patel, Minal
Cai, Qunfeng
Ding, Dalian
Salvi, Richard
Hu, Zihua
Hu, Bo Hua
author_facet Patel, Minal
Cai, Qunfeng
Ding, Dalian
Salvi, Richard
Hu, Zihua
Hu, Bo Hua
author_sort Patel, Minal
collection PubMed
description Acoustic trauma, one of the leading causes of sensorineural hearing loss, induces sensory hair cell damage in the cochlea. Identifying the molecular mechanisms involved in regulating sensory hair cell death is critical towards developing effective treatments for preventing hair cell damage. Recently, microRNAs (miRNAs) have been shown to participate in the regulatory mechanisms of inner ear development and homeostasis. However, their involvement in cochlear sensory cell degeneration following acoustic trauma is unknown. Here, we profiled the expression pattern of miRNAs in the cochlear sensory epithelium, defined miRNA responses to acoustic overstimulation, and explored potential mRNA targets of miRNAs that may be responsible for the stress responses of the cochlea. Expression analysis of miRNAs in the cochlear sensory epithelium revealed constitutive expression of 176 miRNAs, many of which have not been previously reported in cochlear tissue. Exposure to intense noise caused significant threshold shift and apoptotic activity in the cochleae. Gene expression analysis of noise-traumatized cochleae revealed time-dependent transcriptional changes in the expression of miRNAs. Target prediction analysis revealed potential target genes of the significantly downregulated miRNAs, many of which had cell death- and apoptosis-related functions. Verification of the predicted targets revealed a significant upregulation of Taok1, a target of miRNA-183. Moreover, inhibition of miR-183 with morpholino antisense oligos in cochlear organotypic cultures revealed a negative correlation between the expression levels of miR-183 and Taok1, suggesting the presence of a miR-183/Taok1 target pair. Together, miRNA profiling as well as the target analysis and validation suggest the involvement of miRNAs in the regulation of the degenerative process of the cochlea following acoustic overstimulation. The miR-183/Taok1 target pair is likely to play a role in this regulatory process.
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spelling pubmed-35893502013-03-07 The miR-183/Taok1 Target Pair Is Implicated in Cochlear Responses to Acoustic Trauma Patel, Minal Cai, Qunfeng Ding, Dalian Salvi, Richard Hu, Zihua Hu, Bo Hua PLoS One Research Article Acoustic trauma, one of the leading causes of sensorineural hearing loss, induces sensory hair cell damage in the cochlea. Identifying the molecular mechanisms involved in regulating sensory hair cell death is critical towards developing effective treatments for preventing hair cell damage. Recently, microRNAs (miRNAs) have been shown to participate in the regulatory mechanisms of inner ear development and homeostasis. However, their involvement in cochlear sensory cell degeneration following acoustic trauma is unknown. Here, we profiled the expression pattern of miRNAs in the cochlear sensory epithelium, defined miRNA responses to acoustic overstimulation, and explored potential mRNA targets of miRNAs that may be responsible for the stress responses of the cochlea. Expression analysis of miRNAs in the cochlear sensory epithelium revealed constitutive expression of 176 miRNAs, many of which have not been previously reported in cochlear tissue. Exposure to intense noise caused significant threshold shift and apoptotic activity in the cochleae. Gene expression analysis of noise-traumatized cochleae revealed time-dependent transcriptional changes in the expression of miRNAs. Target prediction analysis revealed potential target genes of the significantly downregulated miRNAs, many of which had cell death- and apoptosis-related functions. Verification of the predicted targets revealed a significant upregulation of Taok1, a target of miRNA-183. Moreover, inhibition of miR-183 with morpholino antisense oligos in cochlear organotypic cultures revealed a negative correlation between the expression levels of miR-183 and Taok1, suggesting the presence of a miR-183/Taok1 target pair. Together, miRNA profiling as well as the target analysis and validation suggest the involvement of miRNAs in the regulation of the degenerative process of the cochlea following acoustic overstimulation. The miR-183/Taok1 target pair is likely to play a role in this regulatory process. Public Library of Science 2013-03-05 /pmc/articles/PMC3589350/ /pubmed/23472202 http://dx.doi.org/10.1371/journal.pone.0058471 Text en © 2013 Patel et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Patel, Minal
Cai, Qunfeng
Ding, Dalian
Salvi, Richard
Hu, Zihua
Hu, Bo Hua
The miR-183/Taok1 Target Pair Is Implicated in Cochlear Responses to Acoustic Trauma
title The miR-183/Taok1 Target Pair Is Implicated in Cochlear Responses to Acoustic Trauma
title_full The miR-183/Taok1 Target Pair Is Implicated in Cochlear Responses to Acoustic Trauma
title_fullStr The miR-183/Taok1 Target Pair Is Implicated in Cochlear Responses to Acoustic Trauma
title_full_unstemmed The miR-183/Taok1 Target Pair Is Implicated in Cochlear Responses to Acoustic Trauma
title_short The miR-183/Taok1 Target Pair Is Implicated in Cochlear Responses to Acoustic Trauma
title_sort mir-183/taok1 target pair is implicated in cochlear responses to acoustic trauma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3589350/
https://www.ncbi.nlm.nih.gov/pubmed/23472202
http://dx.doi.org/10.1371/journal.pone.0058471
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