High-throughput sequencing of long non-coding RNA and mRNA expression profiles in post-cardiac arrest mouse hippocampus

Background: Cardiac arrest (CA) is one of the leading lethal factors. Despite cardiopulmonary resuscitation (CPR) procedure has been consecutively improved and lots of new strategies have been developed, neurological outcome of the patients experienced CPR is still disappointing. Here we aimed to identify potential key long non-coding RNAs (lncRNAs) closely related to cognitive deficits in post-cardiac arrest mouse hippocampus.Methods: LncRNA and mRNA expression profiles in hippocampal tissues from CA/CPR and sham mice were analyzed by high-throughput RNA sequencing (RNA-seq). Four pairs of lncRNAs/mRNAs were validated using quantitative real-time PCR (qRT-PCR). Gene ontology (GO) and KEGG pathway enrichment analyses were performed to investigate the functions of deregulated genes. Significant factors of the mainly affected GO terms were measured in the hippocampus. Correlated coding-noncoding co-expression (CNC) network was established to predict lncRNAs function.Results: A total of 1920 differentially expressed lncRNAs and 1162 expressed mRNAs were identified. The qRT-PCR analysis and RNA-seq results were in good agreement. Functional enrichment analyses showed that the differentially expressed genes were mainly associated with inflammatory and apoptotic signaling pathways. Whole body ischemia and reperfusion (I/R) injury-induced inflammatory cytokines and neuronal apoptosis were significantly elevated in hippocampal tissue. Combining CNC analysis and literature validation, we found that lncRNA NONMMUT113601.1 termed lncRNA-PS correlated positively with expression of the inflammation and apoptosis-associated gene Shc1, whose upregulation in brain played a vital role in cerebral ischemia-reperfusion injury. Additionally, lncRNA NONMMUT041306.2 and NONMMUT115748.1 mediated gene expression by binding the inflammation-regulated transcription factor CCAAT/enhancer binding protein (C/EBP).Conclusions: These findings collectively indicated that lncRNAs may have key functions to regulate vital metabolic pathways and processes involved in the development of cognitive deficits in patients undergoing CA/CPR.