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老年小鼠术后认知功能障碍中潜在关键长链非编码RNA的鉴定

Identification of the Potential Key Long Non-coding RNAs in Aged Mice With Postoperative Cognitive Dysfunction.

作者信息

Li Ming, Chen Chan, Zhang Weiyi, Gao Rui, Wang Qiao, Chen Hai, Zhang Shu, Mao Xiaobo, Leblanc Mathis, Behensky Adam, Zhang Zheng, Gan Lu, Yu Hai, Zhu Tao, Liu Jin

机构信息

Department of Anesthesiology and Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, China.

Department of Emergency Medicine, West China Hospital, Sichuan University, Chengdu, China.

出版信息

Front Aging Neurosci. 2019 Jul 17;11:181. doi: 10.3389/fnagi.2019.00181. eCollection 2019.

DOI:10.3389/fnagi.2019.00181
PMID:31379560
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6650538/
Abstract

Postoperative cognitive dysfunction (POCD) is a significant complication of surgery, particularly in elderly patients. Emerging researches showed that long non-coding RNA (lncRNA) may play a vital role in the pathogenesis of POCD. Here we aimed to identify potential key lncRNAs involved in the development of POCD. LncRNA and mRNA expression profiles in hippocampal tissues from POCD and control mice were analyzed by microarray assay. Gene ontology (GO) and KEGG pathway enrichment analyses were conducted to probe the functions of dysregulated genes. Then, important factors of the mainly affected biological processes were measured in the hippocampus. Correlated coding-non-coding co-expression (CNC) networks were constructed. Finally, the potential key pairs of lncRNA and target mRNA implicated in POCD were probed. Our data showed that 868 differentially expressed lncRNAs and 690 differentially expressed mRNAs were identified in total. GO and KEGG analyses indicated that the differentially expressed genes were mainly associated with inflammatory and apoptotic signaling pathways. Surgery-induced inflammatory cytokines and apoptosis were significantly increased in hippocampal tissues of aged mice. In CNC network analysis, we found that LncRNA uc009qbj.1 was positively correlated with apoptosis-associated gene level. LncRNA ENSMUST00000174338 correlated positively with expression of the inflammation and apoptosis-associated gene . LncRNA NONMMUT00000123687 mediated gene expression by binding the inflammation-regulated transcription factor . Our results suggested that these potential key lncRNAs and mRNAs may play a crucial role in the development of POCD through mediating neuronal inflammation or apoptosis.

摘要

术后认知功能障碍(POCD)是手术的一种严重并发症,在老年患者中尤为常见。新出现的研究表明,长链非编码RNA(lncRNA)可能在POCD的发病机制中起关键作用。在此,我们旨在鉴定参与POCD发生发展的潜在关键lncRNA。通过微阵列分析检测POCD小鼠和对照小鼠海马组织中的lncRNA和mRNA表达谱。进行基因本体(GO)和KEGG通路富集分析以探究失调基因的功能。然后,在海马中检测主要受影响生物学过程的重要因子。构建相关的编码-非编码共表达(CNC)网络。最后,探究与POCD相关的lncRNA和靶mRNA的潜在关键对。我们的数据显示,总共鉴定出868个差异表达的lncRNA和690个差异表达的mRNA。GO和KEGG分析表明,差异表达基因主要与炎症和凋亡信号通路相关。手术诱导的炎性细胞因子和凋亡在老年小鼠海马组织中显著增加。在CNC网络分析中,我们发现LncRNA uc009qbj.1与凋亡相关基因水平呈正相关。LncRNA ENSMUST00000174338与炎症和凋亡相关基因的表达呈正相关。LncRNA NONMMUT00000123687通过结合炎症调节转录因子介导基因表达。我们的结果表明,这些潜在的关键lncRNA和mRNA可能通过介导神经元炎症或凋亡在POCD的发生发展中起关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88a5/6650538/bb10a748308f/fnagi-11-00181-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88a5/6650538/56f268643b4f/fnagi-11-00181-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88a5/6650538/4fbcea100fa4/fnagi-11-00181-g002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88a5/6650538/2899b7fa942a/fnagi-11-00181-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88a5/6650538/bb10a748308f/fnagi-11-00181-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88a5/6650538/56f268643b4f/fnagi-11-00181-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88a5/6650538/4fbcea100fa4/fnagi-11-00181-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88a5/6650538/96aa9ad09645/fnagi-11-00181-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88a5/6650538/d8c767eac3ca/fnagi-11-00181-g004.jpg
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