Expression profiling and functional analysis of circular RNAs in vitro model of intermittent hypoxia-induced liver injury.
Expression profiling and functional analysis of circular RNAs in vitro model of intermittent hypoxia-induced liver injury.
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间歇性缺氧肝损伤体外模型环状RNA表达谱及功能分析
DOI：
10.3389/fphys.2022.972407
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发表时间：
2022
影响因子：
4
通讯作者：
中科院分区：
文献类型：
--
作者：
间歇性缺氧（IH）是阻塞性睡眠呼吸暂停（OSA）的一个显著特征，逐渐被认为是肝损伤的一个关键危险因素。环状RNA（circRNA）被认为是多种生物过程的调节因子。然而，没有研究评估circRNA的改变和circRNA在OSA相关肝损伤中的潜在作用。本研究旨在研究IH诱导的肝损伤体外模型中circRNA的表达谱，以及差异表达的circRNA（DE circRNA）的潜在功能特征。将BRL-3A细胞暴露于IH或常氧。流式细胞仪检测细胞凋亡，细胞计数试剂盒检测细胞活力。通过circRNA测序描绘circRNA的表达谱。通过定量实时PCR（qRT-PCR）验证所选择的circRNA。采用京都基因和基因组百科全书（KEGG）途径和基因本体（GO）分析来预测DE circRNA功能。构建circRNA-miRNA-mRNA调控网络。IH处理引起BRL-3A细胞的细胞损伤。在IH处理的BRL-3A细胞中鉴定出98种circRNA失调。其中上调58例，下调40例。Go和KEGG分析表明，DE circRNA主要富集在生物过程中，如NF−kappaB转录因子活性的正调控和昼夜节律夹带、Wnt信号通路、MAPK信号通路和蛋白质输出等通路。选择具有高数目的反向剪接位点的3个上调的circRNA和3个下调的circRNA用于qRT-PCR验证，并且与测序数据一致。预测circRNA 1056和circRNA 805与microRNA相互作用，从而可能调节下游基因。该研究表征了IH诱导的BRL-3A细胞损伤中失调的circRNA谱。DE circRNA可能在IH诱导的肝损伤的病理生理学中起重要作用。本研究结果为进一步研究阻塞性睡眠呼吸暂停相关肝损伤的机制提供了初步依据，并为阻塞性睡眠呼吸暂停相关肝损伤的发病机制提供了新的理论依据。
Intermittent hypoxia (IH) is a prominent feature of obstructive sleep apnea (OSA) which is increasingly recognized as a key risk factor for liver injury. Circular RNAs (circRNAs) has been suggested to act as a regulator of multiple biological processes. However, there is no study evaluating circRNAs alterations and potential role of circRNAs in OSA-related liver injury. The present study aimed to investigate circRNA expression profiles in vitro model of IH-induced liver injury, as well as potential functional characterization of the differentially expressed circRNAs (DE circRNAs). BRL-3A cells were exposed to IH or normoxia. Cell apoptosis and cell viability were evaluated using flow cytometry and cell counting kit-8, respectively. The expression profile of circRNAs was depicted by circRNA sequencing. The selected circRNAs were verified by quantitative real-time PCR (qRT-PCR). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) analyses were employed to predict DE circRNAs functions. The circRNA-miRNA-mRNA regulatory network was constructed. IH treatment caused cell injury in BRL-3A cells. 98 circRNAs were identified as being dysregulated in IH-treated BRL-3A cells. Among them, 58 were up-regulated and 40 were down-regulated. Go and KEGG analyses suggested that the DE circRNAs were predominantly enriched in the biological process such as positive regulation of NF−kappaB transcription factor activity and pathways such as circadian entrainment, Wnt signaling pathway, MAPK signaling pathway, and protein export. 3 up-regulated circRNAs and 3 down-regulated circRNAs with high number of back-splicing sites were chosen for qRT-PCR validation and were consistent with the sequencing data. CircRNA1056 and circRNA805 were predicted to interact with microRNAs that might thereby regulate downstream genes. The study characterized a profile of dysregulated circRNAs in IH-induced BRL-3A cell injury. DE circRNAs may play vital roles in the pathophysiology of IH-induced liver injury. Our findings provide preliminary support for further research in mechanisms and a new theory for the pathogenesis of OSA-related liver injury.
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影响因子：
9
作者：
Wang Z;Zhao Y;Sun R;Sun Y;Liu D;Lin M;Chen Z;Zhou J;Lv L;Tian X;Yao J
通讯作者：
Yao J
慢性间歇性缺氧小鼠模型中肝脏的非靶向代谢组学分析
影响因子：
4
作者：
Chen LD;Huang ZW;Huang YZ;Huang JF;Zhang ZP;Lin XJ
通讯作者：
Lin XJ
circHIPK3 通过海绵 miR-30a 加剧叶酸诱导的肾小管间质纤维化
影响因子：
4
作者：
Wu Y;Luan J;Jiao C;Zhang S;Ma C;Zhang Y;Fu J;Lai EY;Kopp JB;Pi J;Zhou H
通讯作者：
Zhou H
DOI：
10.1261/rna.047126.114
发表时间：
2014-12
期刊：
RNA (New York, N.Y.)
影响因子：
--
作者：
Lasda E;Parker R
通讯作者：
Parker R
影响因子：
4
作者：
Wang, Hong-guang;Yan, Hua;Tong, Xiao-guang
通讯作者：
Tong, Xiao-guang