子痫前期患者内含子多聚腺苷酸化VEGFA-VEGFR2信号通路的富集分析

Genes in VEGFA-VEGFR2 signaling pathway enriched in pre-eclampsia-related intronic polyadenylation

目的分析与子痫前期(PE)相关的转录组内含子多聚腺苷酸化(IPA)现象。方法从GEO数据库中收集到90例PE相关样本的转录组数据。采用STAR比对到人类基因组hg38,利用IPAFinder软件分析比对文件中的IPA现象。Miranda软件进行miRNA靶基因预测。差异表达基因的评估使用edgeR与对数倍数变化>1和调整的P<0.05,通过Clusterprofiler进行功能富集分析。结果血管内皮生长因子A(VEGFA)-血管内皮生长因子受体2(VEGFR2)信号通路中的基因在PE相关的IPA现象中出现富集,且VEGFA-VEGFR2通路中基因表达水平与IPA现象呈负相关。鉴定出LIN28B和AGO2是与IPA位点结合最显著的基序。分析与这些IPA现象相关的miRNA结合位点,发现miR-193b和miR-365a在IPA基因中起核心调控作用。结论VEGFA-VEGFR2信号通路可能通过IPA改变影响PE的发病,子痫前期中IPA相关miRNA和基因表达变化之间有潜在的临床相关联系。

Objective To investigate genes in VEGFA-VEGFR2 signaling pathway enriched in preeclampsia(PE)-related intronic polyadenylation(IPA).Methods The transcriptome data of 90 PE-related samples were collected from the GEO database.STAR alignment was performed to human genome hg38,and IPAFinder software was used to analyze the IPA phenomenon in the alignment files.Miranda software was used to predict miRNA target genes.Differentially expressed genes were evaluated using edgeR with logarithmic fold change>1 and adjusted P<0.05,and functional enrichment analysis was performed via Clusterprofiler.Results Genes in vascular endothelial growth factor A-vascular endothelial growth factor receptor 2(VEGFA-VEGFR2)signaling pathway were enriched in PE-related IPA,and the expression levels of genes in the VEGFA-VEGFR2 pathway were negatively correlated with IPA.LIN28B and AGO2 were identified as the motifs most significantly bound to the IPA site.Analysis of miRNA binding sites associated with these IPA phenomena revealed that miR 193b and miR 365a played a central regulatory role in IPA genes.Conclusion VEGFA-VEGFR2 signaling pathway may affect the pathogenesis of PE through IPA changes,and there is a potential clinical relevance between IPA related miRNA and gene expression changes in preeclampsia.