Construction and analysis of circular RNA-associated competing endogenous RNA network in the hippocampus of aged mice for the occurrence of postoperative cognitive dysfunction.

Construction and analysis of circular RNA-associated competing endogenous RNA network in the hippocampus of aged mice for the occurrence of postoperative cognitive dysfunction.
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DOI:
10.3389/fnagi.2023.1098510
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发表时间:
2023
影响因子:
4.8
通讯作者:
--
中科院分区:
医学2区
文献类型:
--
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环状RNA是高度稳定的单链环状RNA,在大脑中富集。研究表明,circRNA作为竞争性内源性RNA(ceRNA)网络的一部分,在神经退行性疾病和精神疾病中发挥重要作用。然而,circRNA相关的ceRNA网络在术后认知功能障碍(POCD)中的机制尚未阐明。POCD多发生于老年患者,以海马功能障碍为特征。在此,在七氟醚麻醉下对老龄C57 BL/6小鼠进行剖腹探查,并通过Morris水迷宫测试验证POCD模型。对对照组(Con)和手术组的海马进行全转录组测序。在两组之间鉴定出177个DEcircRNA、221个DEmiRNA和2,052个DEmRNAs。用具有与76个DEmiRNA和549个靶DEmRNA的结合位点的92个DEcircRNA建立ceRNA网络。在功能富集分析中,在ceRNA网络中突出了POCD的病理模式:神经细胞中的异常代谢过程,包括氧代谢,可以促进凋亡,进而影响突触功能,这可能破坏神经可塑性,最终导致认知功能和其他行为模式的改变。总之,这种特定的circRNA-miRNAs-mRNAs的ceRNA网络为POCD的调控机制提供了新的见解,并揭示了潜在的治疗基因靶点。
Circular RNAs are highly stable single-stranded circular RNAs and enriched in the brain. Previous studies showed that circRNAs, as part of competing endogenous RNAs (ceRNAs) network, play an important role in neurodegenerative and psychiatric diseases. However, the mechanism of circRNA-related ceRNA networks in postoperative cognitive dysfunction (POCD) has not been elucidated yet. POCD usually occurs in elderly patients and is characterized by hippocampal dysfunction. Here, aged C57BL/6 mice were subjected to exploratory laparotomy under sevoflurane anesthesia, and this POCD model was verified by Morris water maze test. Whole-transcriptome sequencing was performed on the hippocampus of control group (Con) and surgery group. One hundred and seventy-seven DEcircRNAs, 221 DEmiRNAs and 2,052 DEmRNAs were identified between two groups. A ceRNA network was established with 92 DEcircRNAs having binding sites with 76 DEmiRNAs and 549 target DEmRNAs. In functional enrichment analysis, a pathological pattern of POCD was highlighted in the ceRNA network: Abnormal metabolic process in neural cells, including oxygen metabolism, could promote apoptosis and then affect the synaptic function, which may undermine the neural plasticity and eventually lead to changes in cognitive function and other behavioral patterns. In conclusion, this specific ceRNA network of circRNAs–miRNAs–mRNAs has provided novel insights into the regulatory mechanisms of POCD and revealed potential therapeutic gene targets.
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