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{"title"=>"The miR-183/Taok1 Target Pair Is Implicated in Cochlear Responses to Acoustic Trauma", "type"=>"journal", "authors"=>[{"first_name"=>"Minal", "last_name"=>"Patel", "scopus_author_id"=>"55464126700"}, {"first_name"=>"Qunfeng", "last_name"=>"Cai", "scopus_author_id"=>"35209671500"}, {"first_name"=>"Dalian", "last_name"=>"Ding", "scopus_author_id"=>"7201760987"}, {"first_name"=>"Richard", "last_name"=>"Salvi", "scopus_author_id"=>"7005412656"}, {"first_name"=>"Zihua", "last_name"=>"Hu", "scopus_author_id"=>"12774843600"}, {"first_name"=>"Bo Hua", "last_name"=>"Hu", "scopus_author_id"=>"56560473300"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pmid"=>"23472202", "scopus"=>"2-s2.0-84874631476", "doi"=>"10.1371/journal.pone.0058471", "sgr"=>"84874631476", "pui"=>"368465574"}, "id"=>"15a9fd50-9443-39ca-bd82-abc03a5beed0", "abstract"=>"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.", "link"=>"http://www.mendeley.com/research/mir183taok1-target-pair-implicated-cochlear-responses-acoustic-trauma", "reader_count"=>18, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Student > Doctoral Student"=>4, "Researcher"=>6, "Student > Ph. D. Student"=>2, "Student > Master"=>1, "Other"=>2, "Student > Bachelor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Student > Doctoral Student"=>4, "Researcher"=>6, "Student > Ph. D. Student"=>2, "Student > Master"=>1, "Other"=>2, "Student > Bachelor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>4, "Agricultural and Biological Sciences"=>8, "Medicine and Dentistry"=>4, "Pharmacology, Toxicology and Pharmaceutical Science"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>4}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>8}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>4}, "Unspecified"=>{"Unspecified"=>1}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"Egypt"=>1, "Chile"=>1, "Spain"=>1}, "group_count"=>0}

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• http://doi.org/10.1097/MAO.0000000000001073
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• http://doi.org/10.3390/ijms19092836

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Figshare

• {"files"=>["https://ndownloader.figshare.com/files/977613"], "description"=>"<p>(<b>A</b>) Comparison of the ABR thresholds (dB, mean ± SD) measured at three time points: pre-noise exposure and 2 h and 1 d post-noise exposure. The thresholds at the five tested frequencies, 5, 10, 20, 30 and 40 kHz, are presented. (<b>B</b>) A typical image of nuclear staining with propidium iodide in a section of the sensory epithelium from a control cochlea without exposure to noise. OHC1, OHC2 and OHC3 denote the first, second and third rows of OHCs. Bar: 20 µm. (<b>C</b>) Noise-induced morphological changes in sensory cell nuclei in the upper first cochlear turn of the sensory epithelium from a cochlea examined at 1 d post-noise exposure. Similar changes were noted at 2 h post-noise exposure (data not shown). Single arrows point to condensed OHC nuclei showing an increase in staining intensity with or without a decrease in nuclear size. Nuclear condensation is a sign of apoptosis. Double-arrows indicate the areas of missing cells.</p>", "links"=>[], "tags"=>["auditory", "sensory", "apoptosis"], "article_id"=>644777, "categories"=>["Biological Sciences", "Physiology", "Medicine", "Molecular Biology", "Neuroscience", "Cell Biology", "Genetics"], "users"=>["Minal Patel", "Qunfeng Cai", "Dalian Ding", "Richard Salvi", "Zihua Hu", "Bo Hua Hu"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0058471.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Loss_of_auditory_function_and_the_generation_of_sensory_cell_apoptosis_following_exposure_to_noise_/644777", "title"=>"Loss of auditory function and the generation of sensory cell apoptosis following exposure to noise.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-06 08:59:59"}
• {"files"=>["https://ndownloader.figshare.com/files/977615"], "description"=>"<p>(<b>A</b>) The numbers of miRNAs detected in the normal samples (pre-noise exposure), the noise-samples (collected at 2 h post-noise exposure) and both. Cut off C_T value ≤34. (<b>B</b>) The numbers of miRNAs detected in the normal samples (pre-noise exposure), the noise-samples (collected at 1 d post-noise exposure) and both. Cut off C_T value ≤34.</p>", "links"=>[], "tags"=>["diagram", "mirnas", "noise-exposed"], "article_id"=>644778, "categories"=>["Biological Sciences", "Physiology", "Medicine", "Molecular Biology", "Neuroscience", "Cell Biology", "Genetics"], "users"=>["Minal Patel", "Qunfeng Cai", "Dalian Ding", "Richard Salvi", "Zihua Hu", "Bo Hua Hu"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0058471.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Venn_diagram_showing_the_number_of_miRNAs_detected_in_either_noise_exposed_cochleae_control_cochleae_or_both_/644778", "title"=>"Venn diagram showing the number of miRNAs detected in either noise-exposed cochleae, control-cochleae, or both.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-06 09:00:21"}
• {"files"=>["https://ndownloader.figshare.com/files/977617"], "description"=>"<p>(<b>A</b>) miRNAs associated with cell death related GO terms. (<b>B</b>) miRNAs associated with DNA replication, eye development, cell cycle and protein catabolic process GO terms. (<b>C</b>) miRNAs associated with transcription GO terms. (<b>D</b>) miRNAs associated with gene expression GO terms. (<b>E</b>) miRNAs associated with biosynthetic process GO terms. (<b>F</b>) miRNAs associated with protein kinase cascade, phosphorylation and Wnt signaling pathway GO terms. (<b>G</b>) miRNAs associated with cell proliferation GO terms and <b>(H</b>) miRNAs associated with RNA metabolic process GO terms.</p>", "links"=>[], "tags"=>["mirnas", "ontology"], "article_id"=>644779, "categories"=>["Biological Sciences", "Physiology", "Medicine", "Molecular Biology", "Neuroscience", "Cell Biology", "Genetics"], "users"=>["Minal Patel", "Qunfeng Cai", "Dalian Ding", "Richard Salvi", "Zihua Hu", "Bo Hua Hu"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0058471.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Schematic_of_miRNAs_and_their_associated_gene_ontology_GO_biological_process_terms_/644779", "title"=>"Schematic of miRNAs and their associated gene ontology (GO) biological process terms.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-06 09:00:47"}
• {"files"=>["https://ndownloader.figshare.com/files/977620"], "description"=>"<p>Targeting interactions between a total of seven miRNAs (light pink ellipses) and seven mRNAs (light blue rectangles) are depicted. These seven miRNAs which were downregulated 1 d post-noise exposure were found to have a list of target genes in the TargetScan database. The remaining 14 genes (13 downregulated at 1 d post-noise exposure and 1 upregulated at 2 h post-noise exposure) were either not included in the TargetScan database or had limited number of target genes to be sufficient for subsequent target analysis.</p>", "links"=>[], "tags"=>["targeting", "pathway"], "article_id"=>644781, "categories"=>["Biological Sciences", "Physiology", "Medicine", "Molecular Biology", "Neuroscience", "Cell Biology", "Genetics"], "users"=>["Minal Patel", "Qunfeng Cai", "Dalian Ding", "Richard Salvi", "Zihua Hu", "Bo Hua Hu"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0058471.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_miRNA_mRNA_targeting_pathway_map_/644781", "title"=>"miRNA/mRNA targeting pathway map.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-06 09:01:05"}
• {"files"=>["https://ndownloader.figshare.com/files/977621"], "description"=>"<p><i>Nfat5</i> and <i>Map3k2</i> are downregulated and <i>Taok1</i>, <i>Xiap</i> and <i>Bach2</i> are upregulated in the noise-exposed cochleae compared to the normal cochleae. *<i>p</i><0.05, Student’s <i>t</i>-test.</p>", "links"=>[], "tags"=>["mrnas", "examined"], "article_id"=>644782, "categories"=>["Biological Sciences", "Physiology", "Medicine", "Molecular Biology", "Neuroscience", "Cell Biology", "Genetics"], "users"=>["Minal Patel", "Qunfeng Cai", "Dalian Ding", "Richard Salvi", "Zihua Hu", "Bo Hua Hu"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0058471.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Changes_in_expression_levels_of_five_target_mRNAs_examined_1_d_after_noise_exposure_/644782", "title"=>"Changes in expression levels of five target mRNAs examined 1 d after noise exposure.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-06 09:01:21"}
• {"files"=>["https://ndownloader.figshare.com/files/977623"], "description"=>"<p>(<b>A</b>) A typical image taken using confocal microscopy showing Taok1 immunoreactivity (green fluorescence) in IHCs, OHCs, and Hensen cells (HC). (<b>B</b>) The merged image from (A) and nuclear staining (propidium iodide, red fluorescence) in the same region. (<b>C</b>) Image showing Taok1 immunoreactivity in pillar cells (PC) and Deiters cells (DC). Bar: 10 µm. (<b>D</b>) The merged image from (C) and nuclear staining in the same region. (<b>E</b>) The image of negative control tissue tested without the primary antibody exhibiting nuclear propidium iodide staining in the OHCs with no clear green fluorescence in the same region. (<b>F</b>) Western blot analysis of Taok1 expression in the rat cochlea. Gapdh was used as a cochlea tissue-specific loading control. A single band around 150 kDa corresponds to Taok1 and the 36 kDa band corresponds to Gapdh.</p>", "links"=>[], "tags"=>["taok1", "cochlear", "sensory"], "article_id"=>644783, "categories"=>["Biological Sciences", "Physiology", "Medicine", "Molecular Biology", "Neuroscience", "Cell Biology", "Genetics"], "users"=>["Minal Patel", "Qunfeng Cai", "Dalian Ding", "Richard Salvi", "Zihua Hu", "Bo Hua Hu"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0058471.g006"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Immunolabeling_of_Taok1_protein_in_the_cochlear_sensory_epithelium_/644783", "title"=>"Immunolabeling of Taok1 protein in the cochlear sensory epithelium.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-06 09:01:50"}
• {"files"=>["https://ndownloader.figshare.com/files/977630"], "description"=>"<p>(<b>A</b>) A typical cross-section image of an organotypic cochlear explant cultured with fluorescein-conjugated morpholino (24 h) taken using confocal microscopy. Arrows indicate the presence of the fluorescein-conjugated morpholino oligo (green fluorescence) in the cytoplasm of the cells. OHC1, OHC2 and OHC3 indicate the first, second, and third rows of OHCs. HC indicates Hensen cells. (<b>B</b>) DIC image showing the three rows of OHCs, the single row of IHC and the HC in the same region as (A). (<b>C</b>) A typical cross-section image of an organotypic cochlear explant cultured without fluorescein-conjugated morpholino (24 h) to demonstrate the level of auto-fluorescence. Scale bar: 10 µm.</p>", "links"=>[], "tags"=>["images", "cochlear", "organotypic", "explants", "treated", "fluorescein-conjugated", "morpholino"], "article_id"=>644788, "categories"=>["Biological Sciences", "Physiology", "Medicine", "Molecular Biology", "Neuroscience", "Cell Biology", "Genetics"], "users"=>["Minal Patel", "Qunfeng Cai", "Dalian Ding", "Richard Salvi", "Zihua Hu", "Bo Hua Hu"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0058471.g007"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Typical_images_of_cochlear_organotypic_explants_treated_with_fluorescein_conjugated_morpholino_oligo_/644788", "title"=>"Typical images of cochlear organotypic explants treated with fluorescein-conjugated morpholino oligo.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-06 09:03:01"}
• {"files"=>["https://ndownloader.figshare.com/files/977632"], "description"=>"<p>Changes in miR-183 expression in the cochlear explants treated with miR-183^* antisense morpholino. *<i>p</i><0.05, Students <i>t-</i>test.</p>", "links"=>[], "tags"=>["mir-183", "cochlear", "organotypic", "cultures", "treated", "antisense"], "article_id"=>644789, "categories"=>["Biological Sciences", "Physiology", "Medicine", "Molecular Biology", "Neuroscience", "Cell Biology", "Genetics"], "users"=>["Minal Patel", "Qunfeng Cai", "Dalian Ding", "Richard Salvi", "Zihua Hu", "Bo Hua Hu"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0058471.g008"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Downregulation_of_miR_183_in_cochlear_organotypic_cultures_treated_with_antisense_morpholinos_/644789", "title"=>"Downregulation of miR-183 in cochlear organotypic cultures treated with antisense morpholinos.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-06 09:03:29"}
• {"files"=>["https://ndownloader.figshare.com/files/977633"], "description"=>"<p>Expression changes in (A) <i>Egr1</i>, (B) <i>Irs1</i> and (C) <i>Taok1</i> after miR-183* transfection. *<i>p</i><0.05, Students <i>t</i>-test.</p>", "links"=>[], "tags"=>["mirna", "genes", "cochlear", "organotypic", "cultures", "treated", "antisense"], "article_id"=>644790, "categories"=>["Biological Sciences", "Physiology", "Medicine", "Molecular Biology", "Neuroscience", "Cell Biology", "Genetics"], "users"=>["Minal Patel", "Qunfeng Cai", "Dalian Ding", "Richard Salvi", "Zihua Hu", "Bo Hua Hu"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0058471.g009"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Expression_levels_of_miRNA_target_genes_in_cochlear_organotypic_cultures_treated_with_antisense_morpholinos_/644790", "title"=>"Expression levels of miRNA target genes in cochlear organotypic cultures treated with antisense morpholinos.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-06 09:03:42"}
• {"files"=>["https://ndownloader.figshare.com/files/1011648"], "description"=>"<p>NOTE: Significance of analysis of microarrays (SAM), False discovery rate (FDR) <0% at 2 h, FDR<4% at 1 d.</p>", "links"=>[], "tags"=>["mirna", "acoustic"], "article_id"=>672058, "categories"=>["Biological Sciences", "Physiology", "Medicine", "Molecular Biology", "Neuroscience", "Cell Biology", "Genetics"], "users"=>["Minal Patel", "Qunfeng Cai", "Dalian Ding", "Richard Salvi", "Zihua Hu", "Bo Hua Hu"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0058471.t002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Fold_Changes_in_miRNA_Expression_Following_Acoustic_Overstimulation_/672058", "title"=>"Fold Changes in miRNA Expression Following Acoustic Overstimulation.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-03-05 00:34:18"}
• {"files"=>["https://ndownloader.figshare.com/files/1011669"], "description"=>"<p><b>NOTE</b>: miRNAs are ranked based on their expression levels.</p>", "links"=>[], "tags"=>["endogenous"], "article_id"=>672079, "categories"=>["Biological Sciences", "Physiology", "Medicine", "Molecular Biology", "Neuroscience", "Cell Biology", "Genetics"], "users"=>["Minal Patel", "Qunfeng Cai", "Dalian Ding", "Richard Salvi", "Zihua Hu", "Bo Hua Hu"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0058471.t001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_miRNA_expression_levels_C_T_for_the_normal_group_relative_to_endogenous_gene_expression_/672079", "title"=>"miRNA expression levels (ΔC_T) for the normal group relative to endogenous gene expression.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-03-05 00:34:39"}

PMC Usage Stats | Further Information

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Relative Metric

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F1000Prime