Identifying lncRNA- and Transcription Factor-Associated Regulatory Networks in the Cortex of Rats With Deep Hypothermic Circulatory Arrest

Abstract

Long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) are involved in the mechanism underlying cerebral dysfunction after deep hypothermic circulatory arrest (DHCA), although the exact details have not been elucidated. To explore the expression profiles of lncRNAs and miRNAs in DHCA cerebral injury, we determined the lncRNA, miRNA and mRNA expression profiles in the cerebral cortex of DHCA and sham rats. First, a rat model of DHCA was established, and high-throughput sequencing was performed to analyze the differentially expressed RNAs (DERNAs). Then, the principal functions of the significantly deregulated genes were identified using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Expression networks (lncRNAs-miRNAs-mRNAs and transcription factors (TFs)-miRNAs-mRNAs) were also established. Finally, the expression of DERNAs was confirmed by quantitative real-time PCR (RT-qPCR). We identified 89 lncRNAs, 45 miRNAs and 59 mRNAs between the DHCA and sham groups and constructed a comprehensive competitive endogenous RNAs (ceRNAs) network. A TF-miRNA-mRNA regulatory network was also established. Finally, we predicted that Lcorl-miR-200a-3p-Ttr, BRD4-Ccl2 and Ep300-miR-200b-3p-Tmem72 may participate in the pathogenesis of DHCA cerebral injury.