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

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

doi:10.3389/fnagi.2019.00181

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 Vrk2 level. LncRNA ENSMUST00000174338 correlated positively with expression of the inflammation and apoptosis-associated gene Smad7. LncRNA NONMMUT00000123687 mediated gene expression by binding the inflammation-regulated transcription factor Meis2. 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.

Highlights

MATERIALS AND METHODSPostoperative cognitive dysfunction (POCD) is increasingly recognized as an important complication of major surgical procedures, especially in elderly patients (Moller et al, 1998; Newman et al, 2001)
Emerging researches have shown that long non-coding RNA (lncRNA) may be involved in the pathogenesis of POCD, but the underlying mechanisms remain unclear (Wei et al, 2017; Zhang et al, 2018)
This study was an exploratory analysis on which lncRNAs were involved in the pathogenesis of POCD

Summary

Introduction

Postoperative cognitive dysfunction (POCD) is increasingly recognized as an important complication of major surgical procedures, especially in elderly patients (Moller et al, 1998; Newman et al, 2001). It is characterized by a persistent decline of cognitive performance after surgery, such as memory, information processing, and executive dysfunction (Monk and Price, 2011). To date, the specific mechanisms underlying POCD remain unclear. It is urgently needed to explore the molecular mechanisms of POCD for developing potential therapeutic targets for prevention, diagnosis and treatment

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Conclusion