急性心肌梗死中N6-甲基腺苷与铁死亡的相关分析  

Correlation between N6-methyladenosine and ferroptosis in acute myocardial infarction

作　　者：张婷婷 安丽娟 阿孜古丽·古拉木江 再米然·努尔塔 张雅玲 刘刚[2] 罗梅[1] ZHANG Tingting;AN Lijuan;AZIGULI·Gulamujiang;ZAIMIRAN·Nuerta;ZHANG Yaling;LIU Gang;LUO Mei(Department of Cardiology,2.Catheter Laboratory,the Fifth Affiliated Hospital of Xinjiang Medical University,Urumqi,Xinjiang 830001,China)

机构地区：[1]新疆医科大学第五附属医院心血管内科,新疆维吾尔自治区乌鲁木齐市830001 [2]新疆医科大学第五附属医院导管室,新疆维吾尔自治区乌鲁木齐市830001

出　　处：《中国动脉硬化杂志》2025年第2期135-143,共9页Chinese Journal of Arteriosclerosis

基　　金：新疆维吾尔自治区自然科学基金项目(2022D01C323)。

摘　　要：[目的]分析急性心肌梗死(AMI)中N6-甲基腺苷(m^(6)A)与铁死亡的相关性。[方法]从GEO数据库下载两个微阵列数据集GSE34198和GSE59867。对AMI组和对照组进行差异表达基因分析。使用R语言对所筛选出的差异表达基因进行GO、KEGG和GSVA分析。通过机器学习算法对铁死亡相关基因进行DRA、GBM、LASSO、randomForest特征基因筛选。对筛选出的铁死亡核心基因和m^(6)A相关基因的表达数据进行Pearson相关分析,筛选出相关性强的m^(6)A修饰基因和铁死亡相关基因。从新疆医科大学第五附属医院收集AMI和对照全血样本各10例,通过RT-qPCR和Western blot验证相关基因的表达。[结果]从两个数据集中提取出431个共同差异表达基因,GO和KEGG分析显示,其主要富集在TNF信号通路、FoxO信号通路、B细胞受体信号通路等。差异表达基因通过GSVA得到富集通路有铜死亡、网状细胞死亡、内吞细胞死亡、细胞内碱化死亡和铁死亡。通过机器学习算法进行铁死亡相关基因特征基因筛选,从中筛选出19个核心铁死亡相关基因。将筛选出的铁死亡相关基因和m^(6)A相关基因表达数据进行Pearson相关分析,其中LRPPRC-IREB2、LRPPRC-ATG5、YTHDC2-IREB2、HNRNPA2B1-IREB2、YTHDC2-ATG5为相关性最高的5组基因。RT-qPCR和Western blot结果显示,与对照组相比,AMI患者LRPPRC、YTHDC2、HNRNPA2B1、IREB2、ATG5基因的表达均显著降低(P<0.001),与数据库中基因表达情况一致。[结论]在AMI中m^(6)A甲基化和铁死亡存在相关性。通过调节m^(6)A甲基化相关基因可以调控AMI中的铁死亡,为进一步研究该病的发生机制提供了新的思路。Aim To analyze the correlation between N6-methyladenosine(m 6A)and ferroptosis in acute myocardial infarction(AMI).Methods Two microarray datasets GSE34198 and GSE59867 was explored from GEO database.Both AMI and control samples were analyzed for differentially expressed genes.GO,KEGG,and GSVA analysis of the screened differential genes was performed using R.Machine learning was used to screen ferroptosis associated genes for DRA,GBM,LASSO and randomForest characteristic genes.The expression data of the core ferroptosis gene and m 6A-related genes were analyzed by Pearson correlation analysis,and the m 6A modified genes and ferroptosis associated genes with strong correlation were screened.Finally,10 cases of AMI and 10 control whole blood samples from the Fifth Affiliated Hospital of Xinjiang Medical University were collected,and the expression of related genes was verified by RT-qPCR and Western blot.Results 431 common differentially expressed genes were extracted from two datasets,GO and KEGG analysis showed that these genes were mainly enriched in TNF signaling pathway,FoxO signaling pathway and B cell receptor signaling pathway.The enrichment pathways of differentially expressed genes by GSVA were cuproptosis,netotic cell death,entotic cell death,alkaliptosis and ferroptosis.The characteristic genes of ferroptosis associated genes were screened by machine learning,and 19 core ferroptosis associated genes were screened from them.The expression data of ferroptosis associated genes and m 6A-related genes were analyzed by Pearson correlation analysis.LRPPRC-IREB2,LRPPRC-ATG5,YTHDC2-IREB2,HNRNPA2B1-IREB2 and YTHDC2-ATG5 were the most correlated top five genes.The results of RT-qPCR and Western blot showed that the gene expression levels of LRPPRC,YTHDC2,HNRNPA2B1,IREB2 and ATG5 were significantly lower than those of the control group(P<0.001),which was consistent with the gene expression in the database.Conclusion m 6A methylation is associated with ferroptosis in AMI.By regulating m 6A methylation-related genes,

关 键 词：急性心肌梗死 铁死亡 N6-甲基腺苷 生物信息学 

分 类 号：R5[医药卫生—内科学]