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血浆长链非编码 RNA(lncRNA)GAS5 是冠状动脉疾病的一种新生物标志物。

Plasma Long Non-Coding RNA (lncRNA) GAS5 is a New Biomarker for Coronary Artery Disease.

机构信息

Department of Cardiology, The First People's Hospital of Tianmen, Tianmen, Hubei, China (mainland).

出版信息

Med Sci Monit. 2017 Dec 21;23:6042-6048. doi: 10.12659/msm.907118.

Abstract

Our study aimed to investigate the diagnostic value of long non-coding RNA (lncRNA) GAS5 for coronary artery disease (CAD) and to explore the mechanism of the role of GAS5 in CAD. A total of 30 patients with CAD were selected from January 2015 to January 2017 in The First Hospital of Tianmen. In addition, 30 healthy individuals were selected as a control group, and patients with various other types of cardiovascular diseases were also selected. Expression of GAS5 in plasma of all participants was detected by quantitative real-time PCR. Receiver operating characteristic (ROC) curve analysis was performed to investigate the diagnostic value of GAS5 for CAD. Levels of mammalian target of rapamycin (mTOR) and phospho-mTOR (p-mTOR) in human primary coronary artery endothelial cells (HCAECs) were detected by western blotting. Compared with normal healthy people, expression level of lncRNA Novlnc6 was significantly reduced in patients with CAD and diabetes mellitus, but not in patients with other types of cardiovascular diseases, such as hypertension, abnormal aortic aneurysm, viral myocarditis. In addition, the expression level of GAS5 was significantly lower in patients with CAD compared to patients with diabetes mellitus. ROC curve analysis showed that GAS5 may serve as a promising biomarker for CAD. GAS5 knockdown and overexpression showed no significant effect on the level of mTOR) in HCAECs. However, GAS5 knockdown significantly increased the level of phospho-mTOR (p-mTOR), and GAS5 overexpression significantly decreased the level of p-mTOR. Treatment with mTOR inhibitor and activator showed no significant effect on expression of GAS5 in HCAECs. GAS5 plays a role as upstream regulator of the mTOR pathway to participate in the development of CAD. GAS5 was specifically downregulated in patients with CAD, and it may serve as a promising biomarker for CAD.

摘要

我们的研究旨在探讨长链非编码 RNA(lncRNA)GAS5 对冠心病(CAD)的诊断价值,并探讨 GAS5 在 CAD 中的作用机制。从 2015 年 1 月至 2017 年 1 月,我们从天门第一医院选择了 30 例 CAD 患者。此外,还选择了 30 名健康个体作为对照组,并选择了其他各种类型的心血管疾病患者。通过实时定量 PCR 检测所有参与者血浆中 GAS5 的表达。通过接收者操作特征(ROC)曲线分析探讨 GAS5 对 CAD 的诊断价值。通过 Western blot 检测人原代冠状动脉内皮细胞(HCAEC)中哺乳动物雷帕霉素靶蛋白(mTOR)和磷酸化 mTOR(p-mTOR)的水平。与正常健康人相比,CAD 和糖尿病患者的 lncRNA Novlnc6 表达水平明显降低,但高血压、异常主动脉瘤、病毒性心肌炎等其他类型心血管疾病患者的表达水平没有降低。此外,CAD 患者的 GAS5 表达水平明显低于糖尿病患者。ROC 曲线分析表明,GAS5 可能是 CAD 的一种有前途的生物标志物。GAS5 敲低和过表达对 HCAEC 中 mTOR 水平没有显著影响。然而,GAS5 敲低显著增加了 p-mTOR 的水平,GAS5 过表达显著降低了 p-mTOR 的水平。mTOR 抑制剂和激活剂处理对 HCAEC 中 GAS5 的表达没有显著影响。GAS5 作为 mTOR 通路的上游调节剂发挥作用,参与 CAD 的发生发展。GAS5 在 CAD 患者中特异性下调,可能是 CAD 的一种有前途的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c98/5747294/b6dd37f4e6ff/medscimonit-23-6042-g001.jpg

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