冠心病外周血中环状RNA表达谱及分子网络分析

采用circRNA微阵列芯片筛选冠心病人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个冠心病人和6个与之年龄性别配对的健康对照，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miRNA;根据文献报道的参与冠心病发病机制的miRNA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circRNA;对差异表达基因进行GO功能注释及KEGG pathway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，PI3K-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。

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

Objective To analyze the difference of circular RNA expression profiles between coronary heart disease and non-CHD disease. Methods 6 paired 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>2 and p <0.05; GO function annotation and KEGG 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; 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 circRNA 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.