游赣花,龙向淑,宋方,黄晶,田茂波,肖燕,邓世燕,吴强
YOU Ganhua,LONG Xiangshu,SONG Fang,HUANG Jing,TIAN Maobo,XIAO Yan,DENG Shiyan,WU Qiang

• 1:贵州大学医学院
• 2:贵州省食品药品检验所
• 3:贵州省人民医院心内科
• 4:贵州大学人民医院心内科

摘要(Abstract)：

目的:探讨长链非编码RNA(lncRNA)肺腺癌转移相关转录本1(MALAT1)、核糖核酸牛磺酸上调基因1(TUG1)、Ezrin反义RNA1(EZR-AS1)及lncRNA n342419 (MANTIS)在重度冠心病(CHD)患者外周血单个核细胞(PBMC)中的差异表达及临床意义。方法:选取确诊为重度CHD患者35例作为CHD组,同期无CHD的体检人群38例为对照组;收集所有研究对象的临床特征资料,并抽取空腹静脉血8 mL,分别采用全自动生化分析仪和实时定量PCR(RT-qPCR)检测总胆固醇(CHOL)、高密度脂蛋白(HDL-C)、低密度脂蛋白(LDL-C)及4种lncRNA的表达,采用受试者工作特征(ROC)曲线分析4种lncRNA对重度CHD患者的诊断价值。结果:CHD组患者HDL-C水平比对照组体检人群明显降低(P<0.01),MALAT1、TUG1及EZR-AS1的表达比对照组体检者明显升高,但MANTIS的表达则明显降低(P<0.01);ROC曲线结果显示,MALAT1、TUG1、EZR-AS1、MANTIS的AUC分别为0.851(95%CI为0.764～0.938,P<0.01)、0.768(95%CI为0.662～0.875,P<0.01)、0.884(95%CI为0.811～0.957,P<0.01)及0.807(95%CI为0.707～0.907,P<0.01)。结论:MALAT1、TUG1、EZR-AS1及MANTIS在重度CHD患者PBMC中差异性表达与CHD严重程度相关。
Objective: To investigate the expression and clinical significance of long noncoding RNA(lncRNA) metastasis-associated lung adenocarcinoma transcript 1(MALAT1), taurine up-regulated 1(TUG1), Ezrin antisense RNA1(EZR-AS1), and lncRNA n342419(MANTIS) in peripheral blood mononuclear cells(PBMC) of patients with severe coronary heart disease(CHD). Methods: The experiment was divided into two groups, the control group(38 cases) and CHD group(diagnosed 35 cases). Collecting clinical data of all subjects and drawing 8 ml venous blood on an empty stomach to analyze on automatic biochemical analyzer and qRT-PCR for following expressions of CHOL, HDL-C, LDL-C and four types of IncRNA. Adopting subjects ROC curve to analyze diagnostic value of four types of IncRNA on severe CHD patients. Results: Compared with the control group, the expression level of HDL-C of CHD was significantly lowered(P<0.01),MALAT1, TUG1, and EZR-AS1 increased significantly, while the expression of MANTIS decreased sharply(P<0.01). The results of ROC curve showed that the AUC of MALAT1, TUG1, EZR-AS1, and MANTIS were 0.0851(95%CI was 0.764～0.938, P<0.01), 0.768(95%CI was 0.662～0.875, P<0.01), 0.884(95%CI was 0.811～0.957, P<0.01), and 0.807(95%CI was 0.707～0.907, P<0.01), respectively. Conclusion: The differential expression of MALAT1, TUG1, EZR-AS1, and MANTIS in PBMC of patients with severe CHD were closely related with severity of CHD and have the potential to be biomarkers for diagnosis and evaluation of CHD.

关键词(KeyWords)： 冠心病;外周血;单个核细胞;长链非编码RNA;肺腺癌转移相关转录本1;核糖核酸牛磺酸上调基因1;Ezrin反义RNA1;lncRNA n342419
coronary heart disease;peripheral blood;mononuclear cells;long noncoding RNA;metastasis-associated lung adenocarcinoma transcript 1;taurine up-regulated 1;ezrin antisense RNA1;lncRNA n342419

Abstract:

Keywords:

基金项目(Foundation): 贵州省高层次创新型人才培养计划[黔科合人才(2016)4023];; 贵州省科技平台及人才团队计划项目[黔科合平台人才(2017)5405]

作者(Author): 游赣花,龙向淑,宋方,黄晶,田茂波,肖燕,邓世燕,吴强
YOU Ganhua,LONG Xiangshu,SONG Fang,HUANG Jing,TIAN Maobo,XIAO Yan,DENG Shiyan,WU Qiang

DOI: 10.19367/j.cnki.1000-2707.2019.11.013

参考文献(References)：

• [1] LEENING M J,FERKET B S,STEYERBERG E W,et al.Sex differences in lifetime risk and first manifestation of cardiovascular disease:prospective population based cohort study [J].BMJ,2014,349:5992.
• [2] QUINN J J,CHANG H Y.Unique features of long non-coding RNA biogenesis and function [J].Nature Reviews Genetics,2016,17(1):47-62.
• [3] KIM J,PIAO H L,KIM B J,et al.Long noncoding RNA MALAT1 suppresses breast cancer metastasis [J].Nature Genetics,2018,50(12):1705-1715.
• [4] VIERECK J ,THUM T.Circulating noncoding RNAs as biomarkers of cardiovascular disease and injury [J].Circulation Research,2017,120(2):381-399.
• [5] UCHIDA S,DIMMELER S.Long noncoding RNAs in cardiovascular diseases [J].Circulation Research,2015,116(4):737-750.
• [6] CAI Y,YANG Y,CHEN X,et al.Circulating lncRNA OTTHUMT00000387022,from monocytes as a novel biomarker for coronary artery disease[J].Cardiovascular Research,2016,112(3):714-724.
• [7] 汤庆锋,莫文开,刘亚玲.颈动脉超声检测结果与冠心病患者相关危险因素的相关性研究[J].吉林医学,2019,40(9):2009-2011.
• [8] 杨峰,易凡,曹慧青,等.长链非编码RNA研究进展[J].遗传,2014,36(5):456-468.
• [9] SCHMITZ S U,GROTE P,HERRMANN B G.Mechanisms of long noncoding RNA function in development and disease[J].Cellular and Molecular Life Sciences,2016,73(13):2491-2509.
• [10]ZHANG L,ZHOU C,QIN Q,et al.lncRNA LEF1-AS1 regulates the migration and proliferation of vascular smooth muscle cells by targeting miR-544a/PTEN axis[J].Journal of Cellular Biochemistry,2019,20(9):14670-14678.
• [11]LU Q,MENG Q,QI M,et al.Shear-Sensitive lncRNA AF131217.1 Inhibits Inflammation in HUVECs via Regulation of KLF4 [J].Hypertension,2019,73(5):25-34.
• [12]HAN X,WANG Q,WANG Y,et al.Long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1/microRNA-202-3p/periostin axis modulates invasion and epithelial-mesenchymal transition in human cervical cancer [J].Journal of Cellular Physiology,2019,234(8):14170-14180.
• [13]ZHUANG M,ZHAO S,JIANG Z,et al.MALAT1 sponges miR-106b-5p to promote the invasion and metastasis of colorectal cancer via SLAIN2 enhanced microtubules mobility[J].EBioMedicine,2019,41:286-298.
• [14]LI H,ZHU X,HU L,et al.Loss of exosomal MALAT1 from ox-LDL-treated vascular endothelial cells induces maturation of dendritic cells in atherosclerosis development[J].Cell Cycle,2019,18(18):2255-2267.
• [15]ZHU Y,YANG T,DUAN J,et al.MALAT1/miR-15b-5p/MAPK1 mediates endothelial progenitor cells autophagy and affects coronary atherosclerotic heart disease via mTOR signaling pathway [J].Aging (Albany NY),2019,11(4):1089-1109.
• [16]闫百祥.256层螺旋CT检查对冠状动脉狭窄的诊断价值[J].中华心脏与心律电子杂志,2019,7(4):235-237.
• [17]YOUNG T L,MATSUDA T,CEPKO C L.The noncoding RNA taurine upregulated gene 1 is required for differentiation of the murine retina [J].Current Biology,2005,15(6):501-512.
• [18]CHEN C,CHENG G,YANG X,et al.Tanshinol suppresses endothelial cells apoptosis in mice with atherosclerosis via lncRNA TUG1 up-regulating the expression of miR-26a [J].American Journal of Translational Research,2016,8(7):2981-2991.
• [19]YU C,LI L,XIE F,et al.lncRNA TUG1 sponges miR-204-5p to promote osteoblast differentiation through upregulating Runx2 in aortic valve calcification [J].Cardiovascular Research,2018,114(1):168-179.
• [20]ZHANG X D,HUANG G W,XIE Y H,et al.The interaction of lncRNA EZR-AS1 with SMYD3 maintains overexpression of EZR in ESCC cells [J].Nucleic Acids Research,2018,46(4):1793-1809.
• [21]SHI L,TIAN C,SUN L,et al.The lncRNA TUG1/miR-145-5p/FGF10 regulates proliferation and migration in VSMCs of hypertension [J].Biochemical and Biophysical Research Communications,2018,501(3):688-695.
• [22]ZHU Y,FENG Z,JIAN Z,et al.Long noncoding RNA TUG1 promotes cardiac fibroblast transformation to myofibroblasts via miR29c in chronic hypoxia [J].Molecular Medicine Reports,2018,18(3):3451-3460.
• [23]LEISEGANG M S,FORK C,JOSIPOVIC I,et al.Long noncoding RNA MANTIS facilitates endothelial angiogenic function [J].Circulation,2017,136(1):65-79.
• [24]LEISEGANG M S,BIBLI S I,GUNTHER S,et al.Pleiotropic effects of laminar flow and statins depend on the Krüppel-like factor-induced lncRNA MANTIS [J].European Heart Journal,2019,40(30):2523-2533.

文章评论(Comment)：