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识别深低温停循环大鼠皮质中lncRNA与转录因子相关的调控网络。

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

作者信息

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

机构信息

Department of Cardiac Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.

NHC Key Laboratory of Assisted Circulation, Sun Yat-Sen University, Guangzhou, China.

出版信息

Front Genet. 2021 Dec 17;12:746757. doi: 10.3389/fgene.2021.746757. eCollection 2021.

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.

摘要

长链非编码RNA(lncRNAs)和微小RNA(miRNAs)参与了深低温停循环(DHCA)后脑功能障碍的潜在机制,尽管确切细节尚未阐明。为了探究lncRNAs和miRNAs在DHCA脑损伤中的表达谱,我们测定了DHCA大鼠和假手术大鼠大脑皮层中的lncRNA、miRNA和mRNA表达谱。首先,建立了DHCA大鼠模型,并进行高通量测序以分析差异表达的RNA(DERNAs)。然后,使用基因本体论(GO)和京都基因与基因组百科全书(KEGG)通路富集分析来确定显著失调基因的主要功能。还建立了表达网络(lncRNAs-miRNAs-mRNAs和转录因子(TFs)-miRNAs-mRNAs)。最后,通过定量实时PCR(RT-qPCR)确认DERNAs的表达。我们在DHCA组和假手术组之间鉴定出89种lncRNAs、45种miRNAs和59种mRNAs,并构建了一个综合的竞争性内源性RNA(ceRNAs)网络。还建立了一个TF-miRNA-mRNA调控网络。最后,我们预测Lcorl-miR-200a-3p-Ttr、BRD4-Ccl2和Ep300-miR-200b-3p-Tmem72可能参与DHCA脑损伤的发病机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c71c/8719624/aa88fa0b1788/fgene-12-746757-g001.jpg

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