2020 年第 10 期 第 15 卷

冠心病患者血浆环状RNA表达谱分析

Expression profile of plasma circular RNAs in patients with coronary atherosclerotic heart disease

作者：丁汀1曾小莉1李禹龙1马旭1袁慧1张宏家2

英文作者：Ding Ting1 Zeng Xiaoli1 Li Yulong1 Ma Xu1 Yuan Hui1 Zhang Hongjia2

单位：1首都医科大学附属北京安贞医院检验科100029；2首都医科大学附属北京安贞医院心脏外科100029

英文单位：1Department of Clinical Laboratory Beijing Anzhen Hospital Capital Medical University Beijing 100029 China; 2Department of Cardiac Surgery Beijing Anzhen Hospital， Capital Medical University Beijing 100029 China

关键词：冠心病（冠状动脉粥样硬化性心脏病）；基因芯片；环状RNA；生物标志物

英文关键词：Coronaryatheroscleroticheartdisease;Genemicroarray;CircularRNA;Biomarker

• 摘要：

• 目的 探讨冠心病（冠状动脉粥样硬化性心脏病）患者血浆环状RNA的表达谱及其作为冠心病诊断标志物的潜在价值。方法 选取2016年9—12月在首都医科大学附属北京安贞医院心内科住院拟诊为冠心病的6例患者为研究对象。根据冠状动脉造影结果 分为冠心病组和对照组，各3例。提取血浆总RNA，采用环状RNA芯片筛选2组血浆样本中差异表达的环状RNA。运用生物信息学分析对环状RNA可能结合的微小RNA（miRNA）及其可能参与的分子通路进行预测。结果 环状RNA芯片数据显示，与对照组比较，冠心病组血浆中有116个环状RNA呈现差异性表达，其中74个表达上调，42个表达下调（差异表达倍数＞1.2，P＜0.05）。对与这些差异表达环状RNA结合匹配值较高的5个miRNA位点进行预测，最可能与hsa_circ_0007059结合的5个miRNA位点包括miR-23a-3p、miR-6818-3p、miR-23b-3p、miR-6761-5p和miR-4740-3p。GO富集分析结果 发现，hsa_circ_0007059与线粒体组织负调控、丝/苏氨酸蛋白激酶抑制物活性、DNA结合等关系密切。KEGG分析表明hsa_circ_0007059显著富集的分子路径包括甘露糖型O-聚糖生物合成、鞘糖脂生物合成、脂肪酸延伸、嘌呤代谢等。结论 与对照组比较，冠心病患者血浆环状RNA表达谱存在明显差异。hsa_circ_0007059可能与心血管疾病的发生发展有关。

• Objective To investigate the expression profile of plasma circular RNAs (circRNAs) in patients with coronary atherosclerotic heart disease (CHD) and the potential value as a diagnostic marker of CHD. Methods Six patients to be diagnosed with CHD, who were admitted to the department of Cardiology, Beijing Anzhen Hospital, Capital Medical University from September to December 2016 were collected. The patients were divided into CHD group and control group according to the results of coronary angiography, with 3 cases in each group. The total RNA in plasma was extracted; the differentially expressed circRNAs in plasma of two groups were screened by circRNA microarray. Bioinformatics analysis was used to predict the microRNAs (miRNAs) that might bind to certain circRNA and the molecular pathways that might be involved. Results The result of circRNA microarray showed that there were 116 circRNAs in the CHD group.Seventy-four circRNAs were upregulated and 42 circRNAs were downregulated (fold change＞1.2, P＜0.05). Five miRNAs with a high match value for each differential circRNA were predicted. The five miRNAs was possibly related to hsa_circ_0007059 include miR-23a-3p, miR-6818-3p, miR-23b-3p, miR-6761-5p and miR-4740-3p. The results of GO enrichment analysis showed that hsa_circ_0007059 was closely related to negative regulation of mitochondrion, serine/threonine protein kinase inhibitor and DNA binding. The results of KEGG analysis showed that hsa_circ_0007059 was related to molecular pathways including mannose type O-glycan biosynthesis, glycosphingolipid biosynthesis, fatty acid elongation and purine metabolism. Conclusions There are significant differences of circRNAs between patients with CHD and control group. Hsa_circ_0007059 may be related to the occurrence and development of cardiovascular diseases.