Liang Bin, Li Menglan, Deng Qianyun, Wang Chen, Rong Jialing, He Siying, Xiang Yang, Zheng Fang
Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Wuhan, China.
Department of Clinical Laboratory, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China.
Ann Transl Med. 2020 Jun;8(12):741. doi: 10.21037/atm-19-4728.
Circular RNAs (circRNAs) have been reported to aberrantly express in coronary artery disease (CAD). Due to their special structures, circRNAs have the potential to be specific and stable markers. We conducted this study to explore circZNF609's function in atherosclerosis and to evaluate its predictive values for CAD.
About 330 CAD patients and 209 controls were enrolled and the expression of circZNF609 in peripheral blood leukocytes (PBLs) was detected by quantitative real time polymerase chain reaction (RT-PCR). Spearman correlation, multivariate regression, multivariate logistic regression and receiver operating characteristic curve (ROC) were performed. Moreover, circZNF609 was overexpressed in mice macrophage RAW264.7 to investigate its influence on inflammatory cytokines. Finally, bioinformatics analysis was executed to excavate the potential downstream pathway of circZNF609.
The expression level of circZNF609 in PBLs of CAD patients was significantly decreased compared with the controls (the fold changes of 0.4133, P<0.0001). The logistic regression analysis showed that decreased circZNF609 expressions were independently associated with increased risks of CAD. The area under the ROC curve was 0.761 (95% CI: 0.721-0.800, P<0.0001). Furthermore, the circZNF609 expression level was correlated with C-reactive protein (r=-0.138, P=0.026) and lymphocyte counts (r=0.16, P=0.01). After overexpression of circZNF609 in RAW264.7 cells, the expression level of IL-6 (P<0.001) and TNF-α (P<0.01) were significantly decreased and IL-10 was significantly increased (P<0.001). Bioinformatics analysis suggested that the abnormal expression of circZNF609 might probably sponge miRNA to modulate the inflammation cytokines.
CircRNA ZNF609 played an anti-inflammatory role and was an independent protective factor for CAD. It represented a moderate diagnostic value and might provide a new therapeutic target for CAD.
据报道，环状RNA（circRNAs）在冠状动脉疾病（CAD）中异常表达。由于其特殊结构，circRNAs有潜力成为特异性和稳定的标志物。我们开展本研究以探究circZNF609在动脉粥样硬化中的作用，并评估其对CAD的预测价值。
纳入约330例CAD患者和209例对照，采用定量实时聚合酶链反应（RT-PCR）检测外周血白细胞（PBLs）中circZNF609的表达。进行Spearman相关性分析、多变量回归分析、多变量逻辑回归分析及受试者工作特征曲线（ROC）分析。此外，在小鼠巨噬细胞RAW264.7中过表达circZNF609，以研究其对炎性细胞因子的影响。最后，进行生物信息学分析以挖掘circZNF609潜在的下游通路。
与对照组相比，CAD患者PBLs中circZNF609的表达水平显著降低（倍数变化为0.4133，P<0.0001）。逻辑回归分析显示，circZNF609表达降低与CAD风险增加独立相关。ROC曲线下面积为0.761（95%CI：0.721 - 0.800，P<0.0001）。此外，circZNF609表达水平与C反应蛋白（r=-0.138，P=0.026）及淋巴细胞计数（r=0.16，P=0.01）相关。在RAW264.7细胞中过表达circZNF609后，白细胞介素-6（IL-6）（P<0.001）和肿瘤坏死因子-α（TNF-α）（P<0.01）的表达水平显著降低，而白细胞介素-10（IL-10）显著升高（P<0.001）。生物信息学分析表明，circZNF609的异常表达可能通过吸附微小RNA（miRNA）来调节炎性细胞因子。
CircRNA ZNF609发挥抗炎作用，是CAD的独立保护因素。它具有中等诊断价值，可能为CAD提供新的治疗靶点。
