目的: 观察长链非编码RNA(LncRNA)钾离子电压门控通道亚家族q成员1重叠转录1(KCNQ1OT1)在冠状动脉粥样硬化性心脏病(coronary-heart-disease, CHD)中的表达及作用,并探讨其能否成为预测急性心肌梗死(acute myocardial infarction, AMI)的潜在生物学标志物。方法: 入选240例患者,分为AMI组、不稳定型心绞痛(unstable angina pectoris, UAP)组、稳定型心绞痛(stable angina pectoris, SAP)组,非冠心病对照组,每组60例。AMI组于症状发生后6 h采取静脉血,余3组于入院次日清晨采血,血液样本离心后提取上清液冻存以备提取RNA。记录入选患者临床基本资料及心肌损伤标志物、血脂等检验结果,标记其有无高血压及糖尿病病史。实时荧光定量PCR(RT-qPCR)检测患者外周血LncRNA的表达量,绘制ROC曲线并计算曲线下面积以确定LncRNA诊断价值,同时分析其与部分心肌损伤标志物、N末端B型钠尿肽前体(n-terminal pro-B-type natriuretic peptide, NT-proBNP)、左心室射血分数(left ventricular ejection fraction, LVEF)的相关性。结果: (1)LncRNA KCNQ1OT1在AMI组患者血清中的表达明显高于对照组(P<0.05);(2)AMI组患者血清中LncRNA KCNQ1OT1表达与cTnI、CK-MB及NT-proBNP的表达呈正相关,与LVEF%的表达呈负相关;(3)LncRNA KCNQ1OT1的预测能力:AUC为0.793(95% CI:0.727-0.859,灵敏度为60.2%,特异性为90.2%,截断值为1.635)。结论: 血清中高表达的LncRNA KCNQ1OT1可作为AMI诊断及判断预后的生物学标志物。
Objective: To observe the expression and role of long non-coding RNA(LncRNA) potassium voltage-gated channel subfamily q member 1 overlapping transcription 1(KCNQ1OT1) in coronary atherosclerotic heart disease(CHD), and to explore whether it can become a potential biomarker for predicting acute myocardial infarction(AMI). Methods: A total of 240 patients were selected and divided into AMI group, unstable angina pectoris(UAP) group, stable angina pectoris(SAP) group and non-coronary heart disease control group, with 60 cases in each group. Venous blood was collected from the AMI group 6 hours after symptom onset, and blood samples were collected from the other three groups in the early morning of the next day after admission. The supernatant of the blood samples was extracted after centrifugation and frozen for RNA extraction. The basic clinical data, myocardial injury markers, lipid levels and other test results of the selected patients were recorded, and their history of hypertension and diabetes was noted. The expression levels of LncRNA in the peripheral blood of the patients were detected by real-time fluorescence quantitative PCR(RT-qPCR), and the ROC curve was drawn and the area under the curve was calculated to determine the diagnostic value of LncRNA. The correlation between LncRNA and some myocardial injury markers, N-terminal pro-B-type natriuretic peptide(NT-proBNP), and left ventricular ejection fraction(LVEF) was analyzed. Results: (1) The expression of LncRNA KCNQ1OT1 in the serum of AMI patients was significantly higher than that in the control group(P<0.05).(2) The expression of LncRNA KCNQ1OT1 in the serum of AMI patients was positively correlated with the expression of cTnI, CK-MB and NT-proBNP, and negatively correlated with the expression of LVEF%.(3) The predictive ability of LncRNA KCNQ1OT1: AUC was 0.793(95% CI: 0.727 - 0.859), with a sensitivity of 60.2%, a specificity of 90.2%, and a cutoff value of 1.635. Conclusion: The highly expressed LncRNA KCNQ1OT1 in serum can serve as a biological marker for the diagnosis and prognosis assessment of AMI.
[1] Lozano-Vidal N, Bink DI, Boon RA. Long noncoding RNA in cardiac aging and disease[J].J Mol Cell Biol, 2019, 11(10): 860-867.
[2] Wang Y, Yang X, Jiang A, et al. Methylation-dependent transcriptional repression of RUNX3 by KCNQ1OT1 regulates mouse cardiac microvascular endothelial cell viability and inflammatory response following myocardial infarction[J].FASEB J, 2019, 33(12): 13145-13160.
[3] Smid M, Dielis AW, Winkens M, et al. Thrombin generation in patients with a first acute myocardial infarction[J].J Thromb Haemost, 2011, 9(3): 450-456.
[4] 中国心血管健康与疾病报告编写组. 中国心血管健康与疾病报告2021概要[J].心脑血管病防治, 2022, 22(4): 20-36, 40.
[5] 全济坤, 关坤萍. 长链非编码RNA-心肌梗死相关转录本在急性心肌梗死中作用的研究进展[J].中西医结合心脑血管病杂志, 2022, 20(16): 2954-2955.
[6] Katrukha IA, Riabkova NS, Kogan AE, et al. Fragmentation of human cardiac troponin T after acute myocardial infarction[J].Clin Chim Acta, 2023, 542: 117281.
[7] 刘天楠, 井玲, 周立君. LncRNA MALAT1在急性心肌梗死中的作用[J].临床与病理杂志, 2020, 40(11): 3006-3009.
[8] Knuuti J, Wijns W, Saraste A, et al. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes[J].Eur Heart J, 2020, 41(3): 407-477.
[9] 张新超, 于学忠, 陈凤英, 等. 急性冠脉综合征急诊快速诊治指南(2019)[J].中国急救医学, 2019, 39(4): 301-308.
[10] Li J, Tong Y, Zhou Y, et al. LncRNA KCNQ1OT1 as a miR-26a-5p sponge regulates ATG12-mediated cardiomyocyte autophagy and aggravates myocardial infarction[J].Int J Cardiol, 2021, 338: 14-23.
[11] Mitsis A, Gragnano F. Myocardial infarction with and without ST-segment elevation:a contemporary reappraisal of similarities and differences[J].Curr Cardiol Rev, 2021, 17(4): e230421189013.
[12] Shao C, Wang J, Tian J, et al. Coronary artery disease: from mechanism to clinical practice[J].Adv Exp Med Biol, 2020, 1177: 1-36.
[13] Fei B, Zhou H, He Z, et al. KCNQ1OT1 inhibition alleviates high glucose-induced podocyte injury by adsorbing miR-23b-3p and regulating Sema3A[J].Clin Exp Nephrol, 2022, 26(5): 385-397.
[14] Xin H, Li C, Cai T, et al. LncRNA KCNQ1OT1 contributes to hydrogen peroxide-induced apoptosis, inflammation, and oxidative stress of cardiomyocytes via miR-130a-3p/ZNF791 axis[J].Cell Biol Int, 2022, 46(12): 2018-2027.
[15] Chen C, Wei M, Wang C, et al. Long noncoding RNA KCNQ1OT1 promotes colorectal carcinogenesis by enhancing aerobic glycolysis via hexokinase-2[J].Aging(Albany NY), 2020, 12(12): 11685-11697.
[16] Lin ZB, Long P, Zhao Z, et al. Long noncoding RNA KCNQ1OT1 is a prognostic biomarker and mediates CD8(+) T cell exhaustion by regulating CD155 expression in colorectal cancer[J].Int J Biol Sci, 2021, 17(7): 1757-1768.
[17] Chen P, Sun LS, Shen HM, et al. LncRNA KCNQ1OT1 accelerates ovarian cancer progression via miR-125b-5p/CD147 axis[J].Pathol Res Pract, 2022, 239: 154135.
[18] Li J, Gong L, Zhang R, et al. Fibroblast growth factor 21 inhibited inflammation and fibrosis after myocardial infarction via EGR1[J].Eur J Pharmacol, 2021, 910: 174470.
[19] Huang S, Zhang L, Song J, et al. Long noncoding RNA MALAT1 mediates cardiac fibrosis in experimental postinfarct myocardium mice model[J].J Cell Physiol, 2019, 234(3): 2997-3006.
[20] Chen L, Li S, Zhu J, et al. Mangiferin prevents myocardial infarction-induced apoptosis and heart failure in mice by activating the Sirt1/FoxO3a pathway[J].J Cell Mol Med, 2021, 25(6): 2944-2955.