术后神经认知障碍(PND)是老年患者常见的并发症。然而,其发病机制至今仍难以捉摸。最近的研究表明,环状RNA(circularRNA,circRNA)在神经退行性疾病的发生发展中起着重要作用。例如手术后的PND。CircRNA,作为竞争性内源性RNA(ceRNA),主要充当miRNA的分子海绵,以“吸附”microRNA(miRNA)并降低miRNA对靶mRNA的抑制作用。circRNA的测序数据从基因表达综合(GEO)数据库获得。通过生物信息学方法,ciratlas,miRDB,应用miRTarBase和miRwalk数据库构建circRNA-miRNA-mRNA网络并筛选差异表达的mRNA。为了提高数据的准确性,将衰老小鼠随机分为对照组(非PND组)和PND组,并使用高通量测序对其大脑海马组织进行分析。在两组数据中交叉检测到三个关键基因,是Unc13c,Tbx20和St8sia2(作为hub基因),为PND治疗提供新的靶点。根据基因本体论(GO)和京都基因和基因组百科全书(KEGG)途径富集分析的结果,免疫细胞浸润分析,基因集富集分析(GSEA),连通性图(CMap)分析,定量实时聚合酶链反应(qRT-PCR),与中枢神经系统无关的基因被移除,最后,鉴定mmu_circ_0000331/miR-1224-3p/Unc13c和mmu_circ_0000406/miR-24-3p/St8sia2ceRNA网络。此外,CMap方法用于选择具有最大负相关性绝对值的前4个活性化合物,包括西马特罗,Rucaparib,FG-7142和氢化可的松。
Postoperative neurocognitive disorder (PND) is a common complication in older patients. However, its pathogenesis has still remained elusive. Recent studies have shown that circular RNA (circRNA) plays an important role in the development of neurodegenerative diseases, such as PND after surgery. CircRNA, as a competitive endogenous RNA (ceRNA), mainly acts as a molecular sponge for miRNA to \"adsorb\" microRNA (miRNA) and to reduce the inhibitory effects of miRNAs on target mRNA. The sequencing data of circRNA were obtained from the Gene Expression Omnibus (GEO) database. By bioinformatic methods, circAtlas, miRDB, miRTarBase and miRwalk databases were applied to construct circRNA-miRNA-mRNA networks and screen differentially expressed mRNAs. To improve the accuracy of the data, we randomly divided aging mice into control (non-PND group) and PND groups, and used high-throughput sequencing to analyze their brain hippocampal tissue for analysis. Three key genes were cross-detected in the data of both groups, which were Unc13c, Tbx20 and St8sia2 (as hub genes), providing new targets for PND treatment. According to the results of the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, immune cell infiltration analysis, gene set enrichment analysis (GSEA), Connectivity Map (CMap) analysis, quantitative real-time polymerase chain reaction (qRT-PCR), the genes that were not related to the central nervous system were removed, and finally, mmu_circ_0000331/miR-1224-3p/Unc13c and mmu_circ_0000406/miR-24-3p/St8sia2 ceRNA networks were identified. In addition, the CMap method was used to select the top 4 active compounds with the largest negative correlation absolute values, including cimaterol, Rucaparib, FG-7142, and Hydrocortisone.