RNA-seq Profiling and Co-expression Network Analysis of Long Noncoding RNAs and mRNAs Reveal Novel Pathogenesis of Noise-induced Hidden Hearing Loss. (10th May 2020)

• Record Type: Journal Article
• Authors: Wei, Wei; Shi, Xi; Xiong, Wei; He, Lu; Du, Zheng-De; Qu, Tengfei; Qi, Yue; Gong, Shu-Sheng; Liu, Ke; Ma, Xiulan
• Is Part Of: Neuroscience. Volume 434(2020)
• Page Start: 120
• Page End: 135
• Publication Date: 2020-05-10
• Subjects: ABR auditory brain response -- Atf2 activating transcription factor 2 -- Atp2b4 ATPase -- BM basilar membrane -- BP biological process -- Ca2+ transporting plasma membrane 4 -- CC cellular component -- CI confidence intervals -- GAPDH glyceraldehyde-3-phosphate dehydrogenase -- GNAS guanine nucleotide binding protein, alpha stimulating -- GO gene otology -- IHC inner hair cell -- KEGG Kyoko encyclopedia of genes and genomes -- lncRNA long non-coding RNA -- MF molecular function -- Mia2 melanoma inhibitory activity 2 -- NE-1st the first time of noise exposure -- NE-2nd the second time of noise exposure -- NIHHL noise-induced hidden hearing loss -- NIHL noise-induced hearing loss -- NMDS Non-metric Multidimensional Scaling -- OHC outer hair cell -- PBS phosphate-buffered saline -- PTS permanent threshold shift -- qRT-PCR quantitative real-time polymerase chain reaction -- RNA-seq RNA-sequencing -- ROS radical oxygen species -- Sept7 septin 7 -- SGC spiral ganglion cell -- SPL sound pressure level -- Stk39 serine/threonine kinase 39 -- TTS temporary threshold shifts; long noncoding RNA -- mRNA -- pathogenesis -- noise-induced hidden hearing loss; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2020.03.023
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: Adrenergic pathway is most likely to regulate NIHHL revealed by RNA-seq. GNAS is the targeted mRNA in the adrenergic pathway. GNAS functions downstream of Sept7 . GNAS and Sept7 are specifically up regulated in NIHHL. GNAS and Sept7 regulating adrenergic pathway might reveal pathogenesis of NIHHL. Abstract: Noise-induced hidden hearing loss (NIHHL), one of the family of conditions described as noise-induced hearing loss (NIHL), is characterized by synaptopathy following moderate noise exposure that causes only temporary threshold elevation. Long noncoding RNAs (lncRNAs) mediate several essential regulatory functions in a wide range of biological processes and diseases, but their roles in NIHHL remain largely unknown. In order to determine the potential roles of these lncRNAs in the pathogenesis of NIHHL, we first evaluated their expression in NIHHL mice model and mapped possible regulatory functions and targets using RNA-sequencing (RNA-seq). In total, we identified 133 lncRNAs and 522 mRNAs that were significantly dysregulated in the NIHHL model. Gene Ontology (GO) showed that these lncRNAs were involved in multiple cell components and systems including synapses and the nervous and sensory systems. In addition, a lncRNA–mRNA network was constructed to identify core regulatory lncRNAs and transcription factors. KEGG analysis was also used to identify the potential pathways being affected in NIHHL. These analyses allowed us to identify the guanine nucleotide binding protein alpha stimulating ( GNAS ) gene as a key transcription factor and the adrenergic signaling pathway as a key pathway in the regulation of NIHHL pathogenesis. Our study is the first, to our knowledge, to isolate a lncRNA mediated regulatory pathway associated with NIHHL pathogenesis; these observations may provide fresh insight into the pathogenesis of NIHHL and may pave the way for therapeutic intervention in the future.