构建 LncRNA 介导的 ceRNA 网络，探讨心肌梗死的免疫发病机制。
Construction of LncRNA-mediated CeRNA network for investigating the immune pathogenesis of myocardial infarction.
机构信息
Cardiovascular Department, Liuzhou Traditional Chinese Medical Hospital, Liuzhou, China.
Guangxi University of Chinese Medicine, Nanning, China.
出版信息
Medicine (Baltimore). 2024 Mar 8;103(10):e37413. doi: 10.1097/MD.0000000000037413.
BACKGROUND
Myocardial infarction (MI) is a cardiovascular disease that seriously threatens human health. However, an immune-related competitive endogenous RNA (ceRNA) network has not been reported in MI.
METHODS
The GSE66360, GSE19339, GSE97320, GSE61741, and GSE168281 datasets were acquired from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) and differentially expressed miRNAs (DEmiRNAs) from MI patients and healthy controls were screened and an immune-related ceRNA network was constructed. Furthermore, the key long noncoding RNAs(lncRNAs) highly related to the immune mechanism of MI were identified utilizing the random walk with restart algorithm. Finally, the expression of the hub genes was further verified in the GSE66360, GSE19339, and GSE97320 datasets, and quantitativereal-time polymerase chain reaction (qRT-PCR) was performed for the MI patients and healthy controls.
RESULTS
A total of 184 differentially expressed immune-related genes(DE-IRGs) and 432 DE-miRNAs were obtained, and an immune-related ceRNA network comprising 1421 lncRNAs, 61 DE-miRNAs, and 139 DE-IRGs was constructed. According to the order of stress, betweenness, and closeness, NEAT1, KCNQ1OT1, and XIST were identified as key lncRNAs. Moreover, random walk with restart analysis also suggested that NEAT1, KCNQ1OT1, and XIST are key lncRNAs. Subsequently, a ceRNA network of 10 hub genes and 3 lncRNAs was constructed. Finally, we found that the expression of FCER1G and TYROBP significantly differed between MI patients and control individuals in the GSE66360, GSE19339, and GSE97320 datasets. qRT-PCR revealed that the expression of NEAT1, KCNQ1OT1, XIST, FCER1G, and TYROBP was significantly elevated in MI tissue samples compared to healthy control tissue samples.
CONCLUSION
NEAT1, KCNQ1OT1, XIST, FCER1G, and TYROBP are involved in MI and can be used as molecular biomarkers for the screening and diagnosis of MI. Furthermore, the immune system plays an essential role in the onset and progression of MI.
背景
心肌梗死（MI）是一种严重威胁人类健康的心血管疾病。然而，目前尚未报道 MI 中的免疫相关竞争性内源性 RNA（ceRNA）网络。
方法
从基因表达综合数据库（GEO）中获取 GSE66360、GSE19339、GSE97320、GSE61741 和 GSE168281 数据集。筛选 MI 患者和健康对照者的差异表达基因（DEGs）和差异表达 miRNA（DEmiRNAs），构建免疫相关 ceRNA 网络。此外，利用随机游走重启动算法识别与 MI 免疫机制高度相关的关键长链非编码 RNA（lncRNA）。最后，在 GSE66360、GSE19339 和 GSE97320 数据集中进一步验证枢纽基因的表达，并对 MI 患者和健康对照者进行定量实时聚合酶链反应（qRT-PCR）。
结果
获得了 184 个差异表达的免疫相关基因（DE-IRGs）和 432 个 DE-miRNAs，构建了包含 1421 个 lncRNA、61 个 DE-miRNA 和 139 个 DE-IRGs 的免疫相关 ceRNA 网络。根据顺序、介数和接近度，鉴定出 NEAT1、KCNQ1OT1 和 XIST 为关键 lncRNA。此外，随机游走重启动分析也表明，NEAT1、KCNQ1OT1 和 XIST 是关键 lncRNA。随后，构建了包含 10 个枢纽基因和 3 个 lncRNA 的 ceRNA 网络。最后，我们发现 FCER1G 和 TYROBP 在 GSE66360、GSE19339 和 GSE97320 数据集中 MI 患者和对照组之间的表达存在显著差异。qRT-PCR 显示，与健康对照组织样本相比，MI 组织样本中 NEAT1、KCNQ1OT1、XIST、FCER1G 和 TYROBP 的表达显著升高。
结论
NEAT1、KCNQ1OT1、XIST、FCER1G 和 TYROBP 参与了 MI，可作为 MI 筛查和诊断的分子标志物。此外，免疫系统在 MI 的发病和进展中起关键作用。
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