Bioinformatics Analysis Identifies Potential Ferroptosis Key Genes in the Pathogenesis of Intracerebral Hemorrhage.
Bioinformatics Analysis Identifies Potential Ferroptosis Key Genes in the Pathogenesis of Intracerebral Hemorrhage.
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生物信息学分析确定了脑出血发病机制中潜在的铁死亡关键基因。
DOI：
10.3389/fnins.2021.661663
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发表时间：
2021
影响因子：
4.3
通讯作者：
Wang Q
中科院分区：
文献类型：
--
作者：
Liu T;Li X;Cui Y;Meng P;Zeng G;Wang Y;Wang Q
脑出血是一种危险的神经系统疾病。脑出血中铁凋亡的机制尚不清楚。本研究旨在通过生物信息学分析，寻找脑出血患者铁凋亡的关键分子，为脑出血患者提供治疗靶点，进一步探讨脑出血患者铁凋亡的发生机制。GSE 24265从Gene Expression Omnibus（GEO）数据集下载并与铁凋亡基因杂交。共筛选出45个差异表达基因（DEG），其中大部分涉及TNF信号通路和氧化应激反应。通过蛋白质-蛋白质相互作用（PPI）网络分析和TNF信号通路相关基因的筛选构建的关键模块导致以下感兴趣基因的确认：MAPK 1、MAPK 8、TNFAIP 3、ATF 4和SLC 2A 1。MAPK 1是TNF信号通路和氧化应激相关的关键基因之一，可能在脑出血后铁凋亡中发挥重要作用。MAPK 1相关分子包括hsa-miR-15 b-5 P、hsa-miR-93- 5 P、miR-20 b-5 p、SNHG 16、XIST、AC084219.4、RP 11 -379K17.11、CTC-444N24.11、GS1-358P8.4、CTB-89H12.4、RP 4 -773N10.5和FGD 5-AS 1。我们还建立了出血大鼠模型，用于对ICH大鼠进行运动干预，并使用qRT-PCR评估我们感兴趣的基因的表达水平。脑出血后MAPK 1、ATF 4、SLC 2A 1和TNFAIP 3的mRNA水平上调，而MAPK 8下调。跑步机训练增加了抗炎分子TNFAIP 3和SLC 2A 1的表达，减少了MAPK 1，ATF 4和MAPK 8的表达，表明跑步机训练可用作抗氧化治疗以减少神经元铁凋亡。本研究结果表明，MAPK 1相关的mRNA-miRNA-lncRNA相互作用链可能被用作脑出血后铁凋亡发生和进展的生物标志物。
Intracerebral hemorrhage (ICH) is a dangerous neurological disease. The mechanism of ferroptosis in ICH remains unclear. Using bioinformatics analysis, we aimed to identify the key molecules involved in ferroptosis and provide treatment targets for ICH to further explore the mechanism of ferroptosis in ICH. GSE24265 was downloaded from the Gene Expression Omnibus (GEO) dataset and intersected with ferroptosis genes. A total of 45 differentially expressed genes (DEGs) were selected, most of which were involved in the TNF signaling pathway and oxidative stress response. Key modules constructed by the protein–protein interaction (PPI) network analysis and screening of genes related to the TNF signaling pathway led to the confirmation of the following genes of interest: MAPK1, MAPK8, TNFAIP3, ATF4, and SLC2A1. Moreover, MAPK1 was one of the key genes related to TNF signaling and oxidative stress, and it may play an important role in ferroptosis after cerebral hemorrhage. The MAPK1-related molecules included hsa-miR-15b-5P, hsa-miR-93-5P, miR-20b-5p, SNHG16, XIST, AC084219.4, RP11-379K17.11, CTC-444N24.11, GS1-358P8.4, CTB-89H12.4, RP4-773N10.5, and FGD5-AS1. We also generated a hemorrhage rat model, which was used to conduct exercise intervention in ICH rats, and qRT-PCR was used to assess the expression levels of our genes of interest. The mRNA levels after cerebral hemorrhage showed that MAPK1, ATF4, SLC2A1, and TNFAIP3 were upregulated, whereas MAPK8 was downregulated. Treadmill training increased the expression of anti-inflammatory molecules TNFAIP3 and SLC2A1 and reduced the expression of MAPK1, ATF4, and MAPK8, indicating that treadmill training may be utilized as antioxidant therapy to decrease neuronal ferroptosis. The results of this study indicated that the MAPK1-related mRNA–miRNA–lncRNA interaction chain could be potentially employed as a biomarker of the inception and progression of ferroptosis after cerebral hemorrhage.
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通讯作者：
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通讯作者：
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