鉴定环状 RNA Hsa_circ_0001879 和 Hsa_circ_0004104 作为冠心病的新型生物标志物。
Identification of circular RNA Hsa_circ_0001879 and Hsa_circ_0004104 as novel biomarkers for coronary artery disease.
机构信息
Key Laboratory of Cardiovascular Epidemiology & Department of Epidemiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China.
Department of Epidemiology, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Jiangning, Nanjing, 211166, China.
出版信息
Atherosclerosis. 2019 Jul;286:88-96. doi: 10.1016/j.atherosclerosis.2019.05.006. Epub 2019 May 9.
BACKGROUND AND AIMS
The role of circular RNAs (circRNAs) in coronary artery disease (CAD) remains elusive. The aim of the present study was to profile circRNAs expression in CAD patients and assess diagnostics biomarkers for CAD.
METHODS
The circRNA profiles of 24 CAD patients and 7 controls were assessed by microarray. The expression levels of candidate circRNAs were further verified by qRT-PCR in large cohorts. Logistic regression analysis and receiver operating characteristic were conducted to assess the diagnostic value. Gain-of-function approach was used to determine the functional significance of validated circRNA in THP-1-derived macrophages.
RESULTS
A total of 624 circRNAs and 171 circRNAs were significantly upregulated and downregulated, respectively, in CAD patients relative to controls. Hsa_circ_0001879 and hsa_circ_0004104 were validated to be significantly upregulated in large cohorts. The receiver operating characteristics analysis of hsa_circ_0001879 and hsa_circ_0004104 in CAD patients and controls showed that the area under curve was 0.703 (95% confidence interval: 0.656-0.750; p < 0.001) and 0.700 (95% confidence interval: 0.646-0.755; p < 0.001), respectively. The combination of hsa_circ_0001879 and hsa_circ_0004104, together with CAD risk factors, had the better performance to discriminate CAD patients from healthy controls. Overexpression of hsa_circ_0004104 resulted in dysregulation of atherosclerosis-related genes in THP-1-derived macrophages.
CONCLUSIONS
We offered a transcriptome-wide overview of aberrantly expressed circRNAs in CAD patients and identified two novel circRNA biomarkers to diagnose CAD. Upregulation of hsa_circ_0004104 might contribute to the pathogenesis of CAD.
背景与目的
环状 RNA（circRNAs）在冠状动脉疾病（CAD）中的作用仍不清楚。本研究旨在分析 CAD 患者的 circRNA 表达谱，并评估 CAD 的诊断生物标志物。
方法
通过微阵列分析 24 例 CAD 患者和 7 例对照的 circRNA 谱。在大样本中进一步通过 qRT-PCR 验证候选 circRNA 的表达水平。采用逻辑回归分析和受试者工作特征曲线评估诊断价值。采用功能获得方法确定验证后的 circRNA 在 THP-1 衍生巨噬细胞中的功能意义。
结果
与对照组相比，CAD 患者的 circRNA 中共有 624 个显著上调，171 个显著下调。在大样本中验证 hsa_circ_0001879 和 hsa_circ_0004104 显著上调。hsa_circ_0001879 和 hsa_circ_0004104 在 CAD 患者和对照组中的受试者工作特征分析显示，曲线下面积分别为 0.703（95%置信区间：0.656-0.750；p<0.001）和 0.700（95%置信区间：0.646-0.755；p<0.001）。hsa_circ_0001879 和 hsa_circ_0004104 与 CAD 危险因素联合，对区分 CAD 患者和健康对照具有更好的性能。hsa_circ_0004104 的过表达导致 THP-1 衍生巨噬细胞中动脉粥样硬化相关基因的失调。
结论
我们提供了 CAD 患者中异常表达 circRNA 的全转录组概述，并确定了两个新的 circRNA 生物标志物来诊断 CAD。hsa_circ_0004104 的上调可能有助于 CAD 的发病机制。
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