冠心病外周血中环状RNA表达谱及分子网络分析

Expression profile and molecular network analysis of circRNAs in whole blood of patients with coronary heart disease

目的采用circRNA微阵列芯片筛选冠心病患者和健康对照外周血中差异表达的circRNA,分析表达谱特征,为冠心病发生机制提供新思路并寻找血液标志物。方法选取6例冠心病患者和6名与之年龄、性别配对的健康对照者,检测circRNA并进行比较分析,火山图显示差异circRNAs的情况。运用miRanda软件预测对应结合的miRNAs;根据文献报道的参与冠心病发病机制的miRNAs对结果进一步筛选,再利用两组之间FC>2,P<0.05,找出显著差异表达的circRNAs;对差异表达基因进行GO功能注释及KEGGpathway分析,利用cytoscape软件对结合冠心病相关miRNA最多的10个circRNA进行分析,建立circRNA-miRNA-mRNA分子调控网络。结果与对照组相比,病例组外周血中表达显著差异的circRNA有793个;其中上调599个,下调194个。GO分析结果显示主要涉及细胞外基质,内皮细胞分化等方面,KEGG涉及Wnt,P13K-Akt信号通路。网络图共纳入10个circRNAs,17个相关microRNAs以及24个mRNAs形象展现它们之间的相互作用。结论circRNA可能作为miRNA分子海绵调控下游基因参与冠心病发病过程并作为潜在的血液生物标志物。

Objective To analyze the difference of circular RNA expression profiles between coronary heart disease and non-CHD disease.Methods 6paired peripheral blood specimens of CHD were detected using the human circRNA microarray,miranda software was used to predict the circRNA combinative miRNAs. CircRNAs were regarded as differentially expressed with FC>2and P<0.05;GO function annotation and K.EGG pathway analysis were performed on differentially expressed genes.The molecular regulatory network of circRNA- miRNA-mRNA was established by using cytoscape software.Results 793 differently expressed circRNAs were screened out,among which 599 were up-regulated and 194 were down-regulated.Enrichment of functions mainly involved in extracellular matrix and endothelial cell differentiation;KEGG analysis showed these genes participated in CHD related Wnt and PI3K-Akt signaling pathways.A total of 10 circRNAs,17 related microRNAs and 24 mRNAs were included in the molecular regulatory network to demonstrate their interactions. Conclusion cireRNA may regulate the downstream genes involved in the pathogenesis of CHD by acting as a miRNA molecular sponge and may be a CHD potential blood biomarker.