Li Chaowei, Lin Jinhuang, Chen Qingshi, Zhu Yueyong
Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350001, China.
Department of Gastroenterology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China.
Aging (Albany NY). 2024 Mar 21;16(7):6262-6272. doi: 10.18632/aging.205701.
Circular RNAs (circRNAs) have exhibited microRNA sponge activity, related to many important biological processes. Our study attempted to explore the comprehensive changes of circRNAs expression pattern in Obstructive sleep apnea (OSA)-induced liver injury and provide a global perspective of differentially expressed circRNAs (DECs). Then, RT-qPCR was used to confirm the microarray data. Further, gene ontology (GO) and KEGG pathway analysis were performed to annotate the DECs. Finally, the circRNA-miRNA-mRNA interaction network was established to predicted the target genes and target miRNAs of DECs for a stepwise bioinformatics analysis. We revealed a total of eighty DECs. In the meantime, six circRNAs were randomly validated by RT-qPCR. Among these circRNAs, mmu_circRNA_000469, 37851, 38959, 38983, 31665 were up-regulated in both microarray and qRT-PCR tissues, while mmu_circRNA_27565 was down-regulated. GO analysis revealed that circRNAs-target genes were largely related to liver function process such as carboxylic acid metabolic process and negative regulation of mitochondrial membrane potential. Meanwhile, KEGG analysis found that there were 13 pathways related to these circRNAs- target genes. And the most enriched pathway was Natural killer cell mediated cytotoxicity, which strongly suggests that immune responses may be important for the process of OSA-induced liver injury. In addition, four significant DECs (mmu_circRNA_000469, 38959, 38983, 27565) and their target mRNA and target miRNAs were further selected to establish the regulation network. Our study revealed that circRNAs may play a crucial role in OSA-induced liver injury and thus mmu_circRNA_000469, 38959, 38983, 27565 may serve as biomarkers of biological process of OSA-induced liver injury.
环状RNA（circRNAs）已表现出微小RNA海绵活性，与许多重要的生物学过程相关。我们的研究试图探索阻塞性睡眠呼吸暂停（OSA）诱导的肝损伤中circRNAs表达模式的全面变化，并提供差异表达环状RNA（DECs）的整体情况。然后，使用逆转录定量聚合酶链反应（RT-qPCR）来确认微阵列数据。此外，进行基因本体（GO）和京都基因与基因组百科全书（KEGG）通路分析以注释DECs。最后，建立circRNA-微小RNA-信使RNA相互作用网络，以预测DECs的靶基因和靶微小RNA，进行逐步的生物信息学分析。我们共发现了80个DECs。同时，通过RT-qPCR随机验证了6个circRNAs。在这些circRNAs中，mmu_circRNA_000469、37851、38959、38983、31665在微阵列和qRT-PCR组织中均上调，而mmu_circRNA_27565下调。GO分析表明，circRNAs的靶基因在很大程度上与肝功能过程相关，如羧酸代谢过程和线粒体膜电位的负调控。同时，KEGG分析发现有13条通路与这些circRNAs的靶基因相关。最富集的通路是自然杀伤细胞介导的细胞毒性，这强烈表明免疫反应可能对OSA诱导的肝损伤过程很重要。此外，进一步选择了4个显著的DECs（mmu_circRNA_000469、38959、38983、27565）及其靶mRNA和靶微小RNA来建立调控网络。我们的研究表明，circRNAs可能在OSA诱导的肝损伤中起关键作用，因此mmu_circRNA_000469、38959、38983、27565可能作为OSA诱导的肝损伤生物学过程的生物标志物。
