Nrf2基因敲除小鼠海马中环状RNA和长链非编码RNA的差异表达谱及功能预测
Differential Expression Profiles and Functional Prediction of Circular RNAs and Long Non-coding RNAs in the Hippocampus of Nrf2-Knockout Mice.
作者信息
Zhang Run-Jiao, Li Yan, Liu Qing, Gao Yan-Jing, Du Juan, Ma Jun, Sun Shao-Guang, Wang Lei
机构信息
Department of Human Anatomy, Hebei Medical University, Shijiazhuang, China.
School of Nursing, Hebei Medical University, Shijiazhuang, China.
出版信息
Front Mol Neurosci. 2019 Aug 9;12:196. doi: 10.3389/fnmol.2019.00196. eCollection 2019.
BACKGROUND
Nrf2 (nuclear factor, erythroid 2 like 2) is believed to play a major role in neurodegenerative diseases. The present study attempts to investigate the hippocampal circRNA and lncRNA expression profiles associated with Nrf2-mediated neuroprotection.
METHODS
The hippocampal mRNA, circRNA and lncRNA expression profiles of Nrf2 (-/-) mice were determined by a microarray analysis. Bioinformatics analyses, including identification of differentially expressed mRNAs (DEmRNAs), circRNAs (DEcircRNAs) and lncRNAs (DElncRNAs), DEcircRNA-miRNA-DEmRNA interaction network construction, DElncRNA-DEmRNA co-expression network construction, and biological function annotation, were conducted. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to validate the dysregulated expression of circRNAs and lncRNAs derived from the microarray data of the hippocampus of Nrf2 (-/-) mice.
RESULTS
Compared to wild-type Nrf2 (+/+) mice, 412 DEmRNAs (109 up- and 303 down-regulated mRNAs), 1279 DEcircRNAs (632 up- and 647 down-regulated circRNAs), and 303 DElncRNAs (50 up- and 253 down-regulated lncRNAs) were identified in the hippocampus of Nrf2 (-/-) mice. Additionally, in the qRT-PCR validation results, the expression patterns of selected DEcircRNAs and DElncRNAs were generally consistent with results in the microarray data. The DEcircRNA-miRNA-DEmRNA interaction networks revealed that mmu_circRNA_44531, mmu_circRNA_34132, mmu_circRNA_000903, mmu_circRNA_018676, mmu_circRNA_45901, mmu_circRNA_33836, mmu_circRNA_ 34137, mmu_circRNA_34106, mmu_circRNA_008691, and mmu_circRNA_003237 were predicted to compete with 47, 54, 45, 57, 63, 81, 121, 85, 181, and 43 DEmRNAs, respectively. ENSMUST00000125413, NR_028123, uc008nfy.1, AK076764, AK142725, AK080547, and AK035903 were co-expressed with 178, 89, 149, 179, 142, 55, and 112 DEmRNAs in the Nrf2 (-/-) hippocampus, respectively.
CONCLUSION
Our study might contribute to exploring the key circRNAs and lncRNAs associated with Nrf2-mediated neuroprotection.
背景
核因子红细胞2样2（Nrf2）被认为在神经退行性疾病中起主要作用。本研究旨在探究与Nrf2介导的神经保护相关的海马环状RNA（circRNA）和长链非编码RNA（lncRNA）表达谱。
方法
通过微阵列分析确定Nrf2基因敲除（-/-）小鼠海马中的信使核糖核酸（mRNA）、circRNA和lncRNA表达谱。进行生物信息学分析，包括差异表达mRNA（DEmRNA）、circRNA（DEcircRNA）和lncRNA（DElncRNA）的鉴定、DEcircRNA-微小RNA（miRNA）-DEmRNA相互作用网络构建、DElncRNA-DEmRNA共表达网络构建以及生物学功能注释。采用定量实时聚合酶链反应（qRT-PCR）验证源自Nrf2（-/-）小鼠海马微阵列数据的circRNA和lncRNA的表达失调情况。
结果
与野生型Nrf2（+/+）小鼠相比，在Nrf2（-/-）小鼠海马中鉴定出412个DEmRNA（109个上调和303个下调的mRNA）、1279个DEcircRNA（632个上调和647个下调的circRNA）以及303个DElncRNA（50个上调和253个下调的lncRNA）。此外，在qRT-PCR验证结果中，所选DEcircRNA和DElncRNA的表达模式与微阵列数据结果总体一致。DEcircRNA-miRNA-DEmRNA相互作用网络显示，预测mmu_circRNA_44531、mmu_circRNA_34132、mmu_circRNA_000903、mmu_circRNA_018676、mmu_circRNA_45901、mmu_circRNA_33836、mmu_circRNA_34137、mmu_circRNA_34106、mmu_circRNA_008691和mmu_circRNA_003237分别与47、54、45、57、63、81、121、85、181和43个DEmRNA竞争。在Nrf2（-/-）海马中，ENSMUST00000125413、NR_028123、uc008nfy.1、AK076764、AK142725、AK080547和AK035903分别与178、89、149、179、142、55和11个DEmRNA共表达。
结论
我们的研究可能有助于探索与Nrf2介导的神经保护相关的关键circRNA和lncRNA。
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