RNA-seq analysis of the key long noncoding RNAs and mRNAs related to cognitive impairment after cardiac arrest and cardiopulmonary resuscitation
RNA-seq analysis of the key long noncoding RNAs and mRNAs related to cognitive impairment after cardiac arrest and cardiopulmonary resuscitation
复制标题
心脏骤停和心肺复苏后与认知障碍相关的关键长非编码RNA和mRNA的RNA-seq分析
DOI：
10.18632/aging.103495
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发表时间：
2020-07-31
期刊：
影响因子：
5.2
通讯作者：
Liu, Jin
中科院分区：
文献类型：
--
作者：
Chen, Chan;Liu, Changliang;Liu, Jin
心脏骤停（CA）是世界范围内的主要死亡原因。CA和心肺复苏（CPR）后的幸存者在3个月时发展为中度至重度认知障碍，高达60%。越来越多的证据表明长链非编码RNA（lncRNA）在缺血性脑损伤中起着关键作用。本研究旨在鉴定与CA/CPR后早期认知缺陷相关的潜在关键lncRNA。采用高通量RNA测序技术分析CA/CPR组和假手术组海马LncRNA和mRNA的表达谱，共检测到1920条lncRNA和1162条mRNA的差异表达。通过GO和KEGG通路富集分析和编码-非编码共表达网络分析，证实这些差异表达基因主要与炎症或凋亡信号通路相关。通过qRT-PCR和western blot进一步分析其中5对关键的lncRNA-mRNA。我们发现，lncRNANOMMUT113601.1和mRNA Shc 1，炎症和骨质疏松相关基因，表现出最显着的变化，在海马CA/CPR小鼠。原位杂交结果表明，这种lncRNA与mRNA的相关性主要发生在海马神经元中。这些结果表明，lncRNA-mRNA的关键对可能是复苏后早期认知功能障碍的重要调节因子。
Cardiac arrest (CA) is the leading cause of death around the world. Survivors after CA and cardiopulmonary resuscitation (CPR) develop moderate to severe cognitive impairment up to 60% at 3 months. Accumulating evidence demonstrated that long non-coding RNAs (lncRNAs) played a pivotal role in ischemic brain injury. This study aimed to identify potential key lncRNAs associated with early cognitive deficits after CA/CPR. LncRNA and mRNA expression profiles of the hippocampus in CA/CPR or sham group were analyzed via high-throughput RNA sequencing, which exhibited 1920 lncRNAs and 1162 mRNAs were differentially expressed. These differentially expressed genes were confirmed to be primarily associated with inflammatory or apoptotic signaling pathways through GO and KEGG pathway enrichment analysis and coding-noncoding co-expression network analysis. Among which, five key pairs of lncRNA-mRNA were further analyzed by qRT-PCR and western blot. We found that the lncRNANONMMUT113601.1 and mRNA Shc1, an inflammation and apoptosis-associated gene, exhibited the most significant changes in hippocampus of CA/CPR mice. Furthermore, we found that the correlations between this lncRNA and mRNA mainly happened in neurons of hippocampus by in situ hybridization. These results suggested that the critical pairs of lncRNA-mRNA may act as essential regulators in early cognitive deficits after resuscitation.