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环状 RNA 表达谱及在慢性间歇性低氧诱导肾损伤小鼠模型中的功能分析:发病机制的新见解。

CircRNA expression profiles and functional analysis in a mouse model of chronic intermittent hypoxia-induced renal injury: new insight into pathogenesis.

机构信息

Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China.

Department of Radiology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China.

出版信息

PeerJ. 2023 Feb 28;11:e14957. doi: 10.7717/peerj.14957. eCollection 2023.

Abstract

Increasing evidence has demonstrated that circular RNAs (circRNAs) play crucial roles in the pathogenesis of multiple diseases. However, the functions of circRNAs in renal injury induced by obstructive sleep apnea (OSA) are poorly understood. The aim of this current study is to identify the global changes of circRNAs expression in OSA-induced renal damage. The mouse model of OSA treated by chronic intermittent hypoxia (CIH) was established. We assessed the expression profiles of circRNAs in CIH caused renal injury by microarray analysis. Bioinformatic analyses were further performed by us to assess those differentially expressed circRNAs. Quantitative realtime PCR (qRT-PCR) were then conducted to assure the data of microarray. Finally, a circRNA-miRNA -mRNA competing endogenous RNA (ceRNA) regulatory network was constructed. We found 11 upregulated and 13 downregulated circRNAs in CIH-induced renal injury. The qRT-PCR validated that the six selected circRNAs were identical to the results of microarray. Both Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were further employed to annotate the potential functions of dysregulated circRNAs. Finally, we established a ceRNA network to predict the target genes of circRNAs. In general, our results first illustrate that circRNAs are aberrantly expressed in OSA-induced renal injury, which might aid in offering novel genetic insights into this disease and potential therapeutic targets for OSA-associated chronic kidney disease.

摘要

越来越多的证据表明,环状 RNA(circRNA)在多种疾病的发病机制中发挥着关键作用。然而,circRNA 在阻塞性睡眠呼吸暂停(OSA)引起的肾损伤中的功能仍知之甚少。本研究旨在鉴定 OSA 诱导的肾损伤中circRNA 表达的整体变化。通过慢性间歇性缺氧(CIH)建立 OSA 小鼠模型。我们通过微阵列分析评估 CIH 引起的肾损伤中 circRNA 的表达谱。我们进一步进行了生物信息学分析,以评估那些差异表达的 circRNA。然后通过定量实时 PCR(qRT-PCR)验证微阵列数据。最后,构建了 circRNA-miRNA-mRNA 竞争性内源性 RNA(ceRNA)调控网络。我们发现 CIH 诱导的肾损伤中有 11 个上调和 13 个下调的 circRNA。qRT-PCR 验证了 6 个选定的 circRNA 与微阵列结果一致。GO 和 KEGG 分析进一步用于注释失调 circRNA 的潜在功能。最后,我们建立了一个 ceRNA 网络来预测 circRNA 的靶基因。总之,我们的研究结果首次表明,circRNA 在 OSA 诱导的肾损伤中表达异常,这可能有助于为这种疾病提供新的遗传见解,并为 OSA 相关的慢性肾病提供潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edaa/9983420/91e0cc120853/peerj-11-14957-g001.jpg

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