TUG1在急性心肌梗死患者血清中的表达及其对心肌细胞凋亡的影响

Expression of TUG1 in Serum of Patients with Acute Myocardial Infarction and Its Effect on Myocardial Apoptosis

目的 探讨长链非编码RNA牛磺酸上调基因1(TUG1)在急性心肌梗死(AMI)患者血清中的表达及其对心肌细胞凋亡的影响。方法 采用实时荧光定量PCR检测86例AMI患者(观察组)和86例健康受试者(对照组)血清TUG1的表达,采用受试者工作特征曲线(ROC)分析TUG1诊断AMI的价值,采用Pearson检验分析TUG1与心肌肌钙蛋白(cTnI)、肌酸激酶同工酶(CK-MB)的关系,采用双荧光素酶报告基因检测试剂盒检测TUG1与转录因子SRY相关高迁移率族盒蛋白9(SOX9)的靶向调控关系,采用Annexin-V-FITC/PI流式细胞术测定TUG1过表达的人心肌细胞(AC16)的凋亡。结果 观察组血清TUG1 mRNA表达水平显著高于对照组(P<0.001)。血清TUG1诊断AMI的ROC曲线下面积为0.805,灵敏度和特异度分别为93.10%和82.14%。血清TUG1分别与cTnI(r=0.723,P=0.012)和CK-MB(r=0.603,P=0.031)呈正相关。双荧光素酶报告基因检测结果证实SOX9是TUG1的靶基因。H_(2)O_(2)诱导心肌细胞后,转染TUG1-mimic的心肌细胞凋亡率显著升高(P<0.05)。结论 AMI患者TUG1表达水平上升,并靶向抑制SOX9而促进心肌细胞凋亡。

Objective To investigate the expression of long noncoding RNA taurine-upregulated gene 1(TUG1)in serum of patients with acute myocardial infarction(AMI)and its effect on cardiomyocyte apoptosis.Methods The serum expression of TUG1 was detected by real-time fluorescence quantitative PCR in 86 AMI patients(observation group)and 86 healthy subjects(control group).The receiver operating characteristic curve(ROC)was used to analyze the value of TUG1 in diagnosing AMI.The relationships of TUG1 to cardiac troponin I(cTnI)and creatine kinase isoenzyme(CK-MB)were analyzed by Pearson test.The targeted regulatory relationship between TUG1 and SRY-related high mobility group-box gene 9(SOX9)was determined using a dual luciferase reporter gene assay kit.The apoptosis of TUG1-overexpressed human cardiomyocytes(AC16)was measured using annexin-V-FITC/PI flow cytometry.Results The mRNA expression of serum TUG1 in the observation group was higher than that in the control group(P<0.001).The AUC,sensitivity and specificity of TUG1 for diagnosing AMI were 0.805,93.10%and 82.14%,respectively.Serum TUG1 was positively correlated with cTnI(r=0.723,P=0.012)and CK-MB(r=0.603,P=0.031).The dual-luciferase reporter gene assay confirmed that SOX9 was the target gene of TUG1.The apoptosis rate of cardiomyocytes transfected with TUG1-mimic significantly increased after treatment with H_(2)O_(2)(P<0.05).Conclusion TUG1 is highly expressed in AMI patients,and promotes cardiomyocyte apoptosis by targeted inhibition of SOX9.