Wang Wei, Huo Pengwei, Zhang Lei, Lv Gang, Xia Zhongyuan
Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, China.
Department of Anesthesiology, Yulin No.2 Hospital, Yulin, China.
Front Neurosci. 2022 Sep 20;16:972918. doi: 10.3389/fnins.2022.972918. eCollection 2022.
Postoperative cognitive dysfunction (POCD) is a common postoperative neurological complication in elderly patients. Circular RNAs (circRNAs) are abundant in the mammalian brain and can probably regulate cognitive function. However, the competitive endogenous RNA (ceRNA) regulatory network in POCD remains illiterate. Transcriptomic signatures in the hippocampus of POCD mice derived from the Gene Expression Omnibus (GEO) dataset GSE190880, GSE95070, and GSE115440 were used to identify the circRNA, miRNA, and mRNA expression profiles of POCD mice compared with controls, respectively. A set of differentially expressed RNAs, including 119 circRNAs, 33 miRNAs, and 49 mRNAs were identified. Transcript validation showed the enhanced expression of circ_0001634, circ_0001345, and circ_0001493. A ceRNA regulatory network composed of three circRNAs, three miRNAs, and six mRNAs was established. The hub mRNAs in the ceRNA network were further found to be involved in the hormone catabolic process and regulation of canonical Wnt signaling pathway, revealing their crucial role in POCD. Finally, three miRNAs and four mRNAs were verified by qRT-PCR. These results based on bioinformatics and PCR array suggest that circ_0001634/miR-490-5p/Rbm47, circ_0001634/miR-490-5p/Sostdc1, circ_0001634/miR-7001-5p/Sostdc1, circ_0001345/miR-7001-5p/Sostdc1, and circ_0001493/miR-7001-5p/Sostdc1 may be novel diagnostic biomarkers and therapeutic targets for POCD.
术后认知功能障碍(POCD)是老年患者常见的术后神经并发症。环状RNA(circRNA)在哺乳动物大脑中大量存在,可能对认知功能具有调节作用。然而,POCD中的竞争性内源性RNA(ceRNA)调控网络仍不清楚。利用来自基因表达综合数据库(GEO)数据集GSE190880、GSE95070和GSE115440的POCD小鼠海马体转录组特征,分别鉴定与对照组相比POCD小鼠的circRNA、miRNA和mRNA表达谱。共鉴定出一组差异表达的RNA,包括119个circRNA、33个miRNA和49个mRNA。转录本验证显示circ_0001634、circ_0001345和circ_0001493表达增强。构建了一个由三个circRNA、三个miRNA和六个mRNA组成的ceRNA调控网络。进一步发现ceRNA网络中的枢纽mRNA参与激素分解代谢过程和经典Wnt信号通路的调控,揭示了它们在POCD中的关键作用。最后,通过qRT-PCR验证了三个miRNA和四个mRNA。这些基于生物信息学和PCR阵列的结果表明,circ_0001634/miR-490-5p/Rbm47、circ_0001634/miR-490-5p/Sostdc1、circ_0001634/miR-7001-5p/Sostdc1、circ_0001345/miR-7001-5p/Sostdc1和circ_0001493/miR-7001-5p/Sostdc1可能是POCD新的诊断生物标志物和治疗靶点。