Identifying microRNAs involved in degeneration of the organ of corti during age-related hearing loss.

MicroRNAs (miRNAs), a class of short non-coding RNAs that regulate the expression of mRNA targets, are important regulators of cellular senescence and aging. We questioned which miRNAs are involved in age-related degeneration of the organ of Corti (OC), the auditory sensory epithelium that transduce...

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Main Authors: Qian Zhang, Huizhan Liu, Joann McGee, Edward J Walsh, Garrett A Soukup, David Z Z He
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3640032?pdf=render
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author Qian Zhang
Huizhan Liu
Joann McGee
Edward J Walsh
Garrett A Soukup
David Z Z He
author_facet Qian Zhang
Huizhan Liu
Joann McGee
Edward J Walsh
Garrett A Soukup
David Z Z He
author_sort Qian Zhang
collection DOAJ
description MicroRNAs (miRNAs), a class of short non-coding RNAs that regulate the expression of mRNA targets, are important regulators of cellular senescence and aging. We questioned which miRNAs are involved in age-related degeneration of the organ of Corti (OC), the auditory sensory epithelium that transduces mechanical stimuli to electrical activity in the inner ear. Degeneration of the OC is generally accepted as the main cause of age-related hearing loss (ARHL), a progressive loss of hearing in individuals as they grow older. To determine which miRNAs are involved in the onset and progression of ARHL, miRNA gene expression in the OC of two mouse strains, C57BL/6J and CBA/J, was compared at three different ages using GeneChip miRNA microarray and was validated by real-time PCR. We showed that 111 and 71 miRNAs exhibited differential expression in the C57 and CBA mice, respectively, and that downregulated miRNAs substantially outnumbered upregulated miRNAs during aging. miRNAs that had approximately 2-fold upregulation included members of miR-29 family and miR-34 family, which are known regulators of pro-apoptotic pathways. In contrast, miRNAs that were downregulated by about 2-fold were members of the miR-181 family and miR-183 family, which are known to be important for proliferation and differentiation, respectively. The shift of miRNA expression favoring apoptosis occurred earlier than detectable hearing threshold elevation and hair cell loss. Our study suggests that changes in miRNA expression precede morphological and functional changes, and that upregulation of pro-apoptotic miRNAs and downregulation of miRNAs promoting proliferation and differentiation are both involved in age-related degeneration of the OC.
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spelling doaj.art-721f59896d64433a85bca791e1ef7a762022-12-21T22:37:51ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0184e6278610.1371/journal.pone.0062786Identifying microRNAs involved in degeneration of the organ of corti during age-related hearing loss.Qian ZhangHuizhan LiuJoann McGeeEdward J WalshGarrett A SoukupDavid Z Z HeMicroRNAs (miRNAs), a class of short non-coding RNAs that regulate the expression of mRNA targets, are important regulators of cellular senescence and aging. We questioned which miRNAs are involved in age-related degeneration of the organ of Corti (OC), the auditory sensory epithelium that transduces mechanical stimuli to electrical activity in the inner ear. Degeneration of the OC is generally accepted as the main cause of age-related hearing loss (ARHL), a progressive loss of hearing in individuals as they grow older. To determine which miRNAs are involved in the onset and progression of ARHL, miRNA gene expression in the OC of two mouse strains, C57BL/6J and CBA/J, was compared at three different ages using GeneChip miRNA microarray and was validated by real-time PCR. We showed that 111 and 71 miRNAs exhibited differential expression in the C57 and CBA mice, respectively, and that downregulated miRNAs substantially outnumbered upregulated miRNAs during aging. miRNAs that had approximately 2-fold upregulation included members of miR-29 family and miR-34 family, which are known regulators of pro-apoptotic pathways. In contrast, miRNAs that were downregulated by about 2-fold were members of the miR-181 family and miR-183 family, which are known to be important for proliferation and differentiation, respectively. The shift of miRNA expression favoring apoptosis occurred earlier than detectable hearing threshold elevation and hair cell loss. Our study suggests that changes in miRNA expression precede morphological and functional changes, and that upregulation of pro-apoptotic miRNAs and downregulation of miRNAs promoting proliferation and differentiation are both involved in age-related degeneration of the OC.http://europepmc.org/articles/PMC3640032?pdf=render
spellingShingle Qian Zhang
Huizhan Liu
Joann McGee
Edward J Walsh
Garrett A Soukup
David Z Z He
Identifying microRNAs involved in degeneration of the organ of corti during age-related hearing loss.
PLoS ONE
title Identifying microRNAs involved in degeneration of the organ of corti during age-related hearing loss.
title_full Identifying microRNAs involved in degeneration of the organ of corti during age-related hearing loss.
title_fullStr Identifying microRNAs involved in degeneration of the organ of corti during age-related hearing loss.
title_full_unstemmed Identifying microRNAs involved in degeneration of the organ of corti during age-related hearing loss.
title_short Identifying microRNAs involved in degeneration of the organ of corti during age-related hearing loss.
title_sort identifying micrornas involved in degeneration of the organ of corti during age related hearing loss
url http://europepmc.org/articles/PMC3640032?pdf=render
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