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

Mengya Liang,Guangxian Chen,Huayang Li,Zhongkai Wu,Yunqi Liu,Shuangjiao Gan,Zhuoming Zhou,Haoliang Liu,Huawei Wu,Yi Zhang,Quan Liu

doi:10.3389/fgene.2021.746757

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.

Highlights

Deep hypothermia circulatory arrest (DHCA) surgery has been more widely used in clinical practice in recent decades (Griepp et al, 1975)
Many studies have suggested that the noncoding RNA family represented by Long noncoding RNAs (lncRNAs) and miRNAs plays a key regulatory role in the growth and differentiation of neurons, the development of the nervous system and the occurrence of neurological diseases (Liu et al, 2018; Mirzaei et al, 2018)
Wei et al found that miR-29 could reduce neuronal apoptosis and intracellular reactive oxygen species (ROS) by inhibiting the expression of the PUMA gene (Wei et al, 2018). miR-194-5p can directly inhibit the expression of the SUMO gene and promote the death of neurons

Summary

Introduction

Deep hypothermia circulatory arrest (DHCA) surgery has been more widely used in clinical practice in recent decades (Griepp et al, 1975). Compared with cardiopulmonary bypass (CPB), DHCA reduces the core temperature to 18°C, which can reduce the body metabolic rate and tissue oxygen consumption and improve organ tolerance to ischemia, thereby substantially reducing the risk of surgery. Previous studies reported neurological dysfunction in 5.3–25% of lncRNA-Associated Networks in DHCA patients after DHCA (Leshnower et al, 2010; Hu et al, 2014; Leshnower et al, 2015; Centofanti et al, 2016). Many studies have reported the effects of intraoperative cerebral perfusion strategies and temperature management for cerebral protection (Apostolakis and Shuhaiber, 2007; Fan et al, 2019); the mechanism of neurologic morbidities has not been fully elucidated, and further investigations are warranted

Objectives

Methods

Results

Conclusion