Awang Danzeng, Danzeng Kanzi, Wang Tianheng, Deji Quzong, Huang Mengting, Ren Hailong, Liu Xinzhu, Zhao Binghan, Gongga Lanzi
Medical College, Tibet University, Department of Clinical Medicine, Lhasa, China; Tibet University, Medical College, Lhasa, China.
Lhasa People's Hospital, Children's Surgery Department, Lhasa, China.
Braz J Otorhinolaryngol. 2025 Mar-Apr;91(2):101557. doi: 10.1016/j.bjorl.2024.101557. Epub 2025 Jan 27.
High altitude hypobaric hypoxia can induce hearing impairment and hearing acclimatization, but few studies have been performed to decipher the potential transition between the two states. To decipher transition-related circular RNAs (circRNAs)-microRNAs (miRNAs)-messenger RNA (mRNAs) regulatory network.
Wistar rats were airlifted from plain to high altitude and maintained for 30 days and 60 days. Hearing acclimatization was determined using the Auditory Brainstem Response (ABR) test. Cochlea tissues were isolated, and high-throughput circRNA analysis and mRNAs-sequencing were performed. Differentially Expressed circRNAs (DEcircRNAs) and Differentially Expressed mRNAs (DEmRNAs) were obtained, and circRNA-miRNA and miRNA-mRNA regulation were predicted. A circRNA-miRNA-mRNA competing endogenous RNA (ceRNA) network was also constructed. The DEmRNAs in this network were functionally annotated using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses based on Metascape.
The ABR assay indicated that hearing impairment happened on day 30 and hearing acclimatization occurred on day 60. Hearing impairment-related circRNAs (64 upregulated and 147 downregulated) and genes (572 upregulated and 757 downregulated) were identified. Hearing acclimatization-related circRNAs (79 upregulated and 142 downregulated) and genes (690 upregulated and 751 downregulated) were also identified. Hearing impairment and hearing acclimatization ceRNA networks were also constructed after integrating the predicted miRNA regulation analyses. Anterograde trans-synaptic signaling (GO:0098916) and negative regulation of cellular response to growth factor stimulus (GO:0090288) were regulated by hearing impairment ceRNA networks, and embryonic organ development (GO:0048568) was regulated by hearing acclimatization ceRNA networks.
Hearing impairment- and hearing acclimatization-associated circRNAs and ceRNA networks were identified, which contribute new knowledge to our understanding of acclimatization transition.
高原低压缺氧可导致听力损伤和听力习服，但很少有研究来解读这两种状态之间的潜在转变。旨在解读与转变相关的环状RNA（circRNA）-微小RNA（miRNA）-信使RNA（mRNA）调控网络。
将Wistar大鼠从平原空运至高原，并分别饲养30天和60天。采用听性脑干反应（ABR）测试确定听力习服情况。分离耳蜗组织，进行高通量circRNA分析和mRNA测序。获得差异表达的circRNA（DEcircRNA）和差异表达的mRNA（DEmRNA），并预测circRNA-miRNA和miRNA-mRNA调控关系。还构建了circRNA-miRNA-mRNA竞争性内源RNA（ceRNA）网络。基于Metascape，使用基因本体论和京都基因与基因组百科全书分析对该网络中的DEmRNA进行功能注释。
ABR检测表明，第30天出现听力损伤，第60天出现听力习服。鉴定出与听力损伤相关的circRNA（上调64个，下调147个）和基因（上调572个，下调757个）。还鉴定出与听力习服相关的circRNA（上调79个，下调142个）和基因（上调690个，下调751个）。整合预测的miRNA调控分析后，还构建了听力损伤和听力习服ceRNA网络。听力损伤ceRNA网络调控顺行性跨突触信号传导（GO:0098916）和细胞对生长因子刺激的反应的负调控（GO:0090288），听力习服ceRNA网络调控胚胎器官发育（GO:0048568）。
鉴定出与听力损伤和听力习服相关的circRNA和ceRNA网络，为我们理解习服转变提供了新知识。
