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.

中文翻译：

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长序列非编码RNA和mRNA的RNA序列分析和共表达网络分析揭示了噪声诱发的隐性听力损失的新型发病机制。

噪声诱发的隐性听力损失（NIHHL）是被描述为噪声诱发的听力损失（NIHL）的一系列疾病之一，其特征在于中度噪声暴露后仅引起暂时阈值升高的突触病。长的非编码RNA（lncRNA）在广泛的生物学过程和疾病中介导了几种基本的调节功能，但是它们在NIHHL中的作用仍然未知。为了确定这些lncRNA在NIHHL发病机理中的潜在作用，我们首先评估了它们在NIHHL小鼠模型中的表达，并使用RNA测序（RNA-seq）绘制了可能的调控功能和靶标。总共，我们确定了在NIHHL模型中明显失调的133个lncRNA和522个mRNA。基因本体论（GO）表明，这些lncRNA参与了多个细胞成分和系统，包括突触以及神经和感觉系统。另外，构建了lncRNA-mRNA网络以鉴定核心调控lncRNA和转录因子。KEGG分析还用于确定NIHHL中受影响的潜在途径。这些分析使我们能够确定鸟嘌呤核苷酸结合蛋白α刺激（GNAS）基因为关键转录因子，而肾上腺素信号传导途径为调控NIHHL发病机理的关键途径。就我们所知，我们的研究是第一个分离与NIHHL发病机制相关的lncRNA介导的调控途径的研究；这些观察结果可能为NIHHL的发病机理提供新的见解，并可能为将来的治疗干预铺平道路。