CircRNA-miRNA-mRNA regulatory network in high-altitude hypobaric hypoxia-induced hearing impairment and hearing acclimatization

IF 1.8 4区医学 Q2 OTORHINOLARYNGOLOGY Brazilian Journal of Otorhinolaryngology Pub Date : 2025-03-01 Epub Date: 2025-01-27 DOI:10.1016/j.bjorl.2024.101557

Danzeng Awang , Kanzi Danzeng , Tianheng Wang , Quzong Deji , Mengting Huang , Hailong Ren , Xinzhu Liu , Binghan Zhao , Lanzi Gongga

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Abstract

Objective

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.

Methods

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.

Results

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.

Conclusion

Hearing impairment- and hearing acclimatization-associated circRNAs and ceRNA networks were identified, which contribute new knowledge to our understanding of acclimatization transition.

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CircRNA-miRNA-mRNA调控网络在高原低气压缺氧致听力损伤和听力适应中的作用。

目的：高原低气压缺氧可诱发听力损伤和听力适应，但目前很少有研究揭示这两种状态之间的潜在转变。破译过渡相关环状RNA (circRNAs)-微RNA (miRNAs)-信使RNA （mrna）调控网络。方法：将Wistar大鼠从平原空运至高原，饲养30 d和60 d。采用听觉脑干反应（ABR）试验测定听力适应。分离耳蜗组织，进行高通量环状rna分析和mrna测序。获得差异表达circRNAs （DEcircRNAs）和差异表达mrna (demmrnas)，并预测circRNA-miRNA和miRNA-mRNA的调控。构建了circRNA-miRNA-mRNA竞争内源RNA （ceRNA）网络。使用基因本体和基于metscape的京都基因与基因组百科全书对该网络中的demrna进行功能注释。结果：ABR测定提示大鼠在第30天出现听力障碍，第60天出现听力适应。鉴定出与听力损伤相关的环状rna（64个上调，147个下调）和基因（572个上调，757个下调）。还鉴定了听力适应相关的环状rna（79个上调，142个下调）和基因（690个上调，751个下调）。在整合预测的miRNA调控分析后，也构建了听力障碍和听力适应的ceRNA网络。顺行跨突触信号通路（GO:0098916）和细胞对生长因子刺激反应的负调控（GO:0090288）受听力损伤ceRNA网络调控，胚胎器官发育（GO:0048568）受听力适应ceRNA网络调控。结论：发现了听力损伤和听力适应相关的circrna和ceRNA网络，为我们理解适应过渡提供了新的知识。

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来源期刊

Brazilian Journal of Otorhinolaryngology OTORHINOLARYNGOLOGY-

CiteScore

3.00

自引率

0.00%

发文量

205

审稿时长

4-8 weeks

期刊介绍： Brazilian Journal of Otorhinolaryngology publishes original contributions in otolaryngology and the associated areas (cranio-maxillo-facial surgery and phoniatrics). The aim of this journal is the national and international divulgation of the scientific production interesting to the otolaryngology, as well as the discussion, in editorials, of subjects of scientific, academic and professional relevance. The Brazilian Journal of Otorhinolaryngology is born from the Revista Brasileira de Otorrinolaringologia, of which it is the English version, created and indexed by MEDLINE in 2005. It is the official scientific publication of the Brazilian Association of Otolaryngology and Cervicofacial Surgery. Its abbreviated title is Braz J Otorhinolaryngol., which should be used in bibliographies, footnotes and bibliographical references and strips.