系统性红斑狼疮患者血浆miRNA-23a表达的检测及意义

摘要
图/表
参考文献
相关文章 (0)

全文: PDF (1592 KB) HTML (1 KB)
输出: BibTeX | EndNote (RIS)

摘要目的：分析miR-23a在系统性红斑狼疮（SLE）患者血浆中的表达及临床意义。方法：收集54例SLE患者、16例类风湿性关节炎（RA）患者和20例健康对照血浆标本，抽提血浆小RNA，反转录后，以cel-miR-39为外参，通过定量PCR检测血浆miR-23a的表达，统计分析miR-23a表达水平与临床资料的相关性。结果：miR-23a在SLE患者、健康对照和RA患者血浆中的相对表达量差异具有统计学意义（x2=39.199，P＜0.001）。与RA患者及健康对照比较，SLE患者血浆中miR-23a表达水平明显下调（P＜0.05）。受试者工作特征曲线（ROC曲线）分析显示，血浆miR-23a区分SLE患者和健康对照以及RA患者的ROC曲线下面积（AUC）分别为0.931和0.884。血浆miR-23a表达水平以19.22临界值区分SLE患者和健康对照的特异性和敏感性达74.5%和88.9%；以30.98临界值区分SLE与RA患者的特异性和敏感性达73.3%和86.3%。血浆miR-23a的表达水平与SLE临床检测指标的相关性分析显示，血浆miR-23a的表达水平与抗核抗体（ANA）滴度水平及血白细胞计数（P＜0.05）相关。结论：SLE患者血浆中下调表达的miR-23a可能与其发病和病情进展相关，是SLE临床诊断一个新的生物学指标。

	服务
	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章
	叶璐璐
	范超凡
	黄茜茜
	郭刚强
	章慧娣
	张丽芳
	林巧爱
	薛向阳

关键词 ：系统性红斑狼疮；微小RNA；miR-23a

Abstract：Objective: To explore miR-23a expression and its clinical significance in the plasma of systemic lupus erythematosus (SLE) patients. Methods: Plasma samples from 54 SLE patients, 16 rheumatoid arthritis (RA) patients and 20 healthy controls were collected. The small RNAs in these plasma samples were isolated and reversely transcribed. Using cel-miR-39 as the external reference, the levels of miR-23a expression were detected with real-time polymerase chain reaction (PCR) method. The correlation between the levels of miR-23a expression and the clinical pathological features of SLE and biological significance of miR-23a expression in SLE were further analyzed with statistical methods. Results: Our data indicated that the levels of miR-23a expression in the plasma of SLE patients, RA patients and healthy controls were significantly different (x2=39.199, P<0.001). The level of miR-23a in the plasma of SLE patients was statistically lower than that in RA patients and healthy controls (P<0.05). The area under the ROC (receiver-operating characteristic) curve (AUC) was 0.931 for discriminating between SLE patients and normal subjects and 0.884 for discriminating between SLE and RA patients and patients. The levels of miR-23a expression were set the cutoff values of 19.22 for healthy control and 30.98 for RA patients, the diagnostic sensitivity and specificity were 74.5%, 88.9%, and 73.3%, 86.3%, respectively. The analysis of the correlation between miR-23a expression and the clinical pathological features of SLE shown that the levels of plasma miR-23a expression had positively correlated with anti-ANA titers and negatively correlated with white blood cell count (P<0.05). Conclusion: Down-regulated of miR-23a expression in plasma of SLE may be involved in the SLE disease occurrence or development and can be used as a novel potential diagnostic biomarker for SLE.

Key words： systemic lupus erythematosus microRNA miR-23a

收稿日期: 2015-09-14

基金资助:浙江省自然科学基金资助项目（LY12H05003，LY15H100004）；浙江省科技厅科研基金资助项目（2012C 33126）；浙江省大学生新苗人才计划（2014R413058，2015R413027，2015R413069）。

通讯作者: 薛向阳，副教授，Email：wyxyy001@163.com。

作者简介: 叶璐璐（1989-），女，安徽安庆人，硕士生。

链接本文:

https://xb.wmu.edu.cn/CN/ 或 https://xb.wmu.edu.cn/CN/Y2016/V46/I3/168

[1] HERRMANN M, VOLL R E, KALDEN J R. Etiopathogenesis of systemic lupus erythematosus[J]. Immunol Today, 2000, 21(9): 424-426.
[2] WAKELAND E K, LIU K, GRAHAM R R, et al. Delineating the genetic basis of systemic lupus erythematosus[J].Immunity, 2001, 15(3): 397-408.
[3] ILLEI G G, TACKEY E, LAPTEVA L, et al. Biomarkers in systemic lupus erythematosus: II. Markers of disease activity[J]. Arthritis Rheum, 2004, 50(7): 2048-2065.
[4] ROVIN B H, BIRMINGHAM D J, NAGARAJA H N, et al. Biomarker discovery in human SLE nephritis[J]. Bull NYU Hosp Jt Dis, 2007, 65(3): 187-193.
[5] LIU C C, MANZI S, AHEARN J M. Biomarkers for sys-temic lupus erythematosus: a review and perspective[J]. Curr Opin Rheumatol, 2005, 17(5): 543-549.
[6] ABULABAN K M, BRUNNER H I. Biomarkers for childhood-onset systemic lupus erythematosus[J]. Curr Rheumatol Rep, 2015, 17(1): 471.
[7] RUVKUN G. Molecular biology. Glimpses of a tiny RNA world[J]. Science, 2001, 294(5543): 797-799.
[8] BARTEL D P. MicroRNAs: genomics, biogenesis, mechanism, and function[J]. Cell, 2004, 116(2): 281-297.
[9] PICASCIA A, GRIMALDI V, PIGNALOSA O, et al. Epigenetic control of autoimmune diseases: from bench to bedside[J]. Clin Immunol, 2015, 157(1):1-15.
[10] SIMPSON L J, ANSEL K M. MicroRNA regulation of lymphocyte tolerance and autoimmunity[J]. J Clin Invest,2015, 125(6): 2242-2249.
[11] HA T Y. MicroRNAs in human diseases: from autoimmune diseases to skin, psychiatric and neurodegenerative diseases[J]. Immune Netw, 2011, 11(5): 227-244.
[12] 陈阿琼, 薛向阳, 章丽和, 等. miR-16在系统性红斑狼疮血浆中的表达及意义[J]. 温州医学院学报, 2013, 43(1): 106-111.
[13] 陈芳, 陈朝生, 章慧娣, 等. 系统性红斑狼疮患者外周血B淋巴细胞中狼疮活动相关miRNA的筛选[J]. 温州医学院学报, 2013, 43(2): 26-30.
[14] CERIBELLI A, YAO B, DOMINGUEZ-GUTIERREZ P R, et al. MicroRNAs in systemic rheumatic diseases[J]. Arthritis Res Ther, 2011, 13(4): 229.
[15] QU B, SHEN N. miRNAs in the pathogenesis of systemic lupus erythematosus[J]. Int J Mol Sci, 2015, 16(5): 9557-9572.
[16] WEBER J A, BAXTER D H, ZHANG S, et al. The microRNA spectrum in 12 body fluids[J]. Clin Chem, 2010, 56(11):1733-1741.
[17] PARK N J, ZHOU H, ELASHOFF D, et al. Salivary microRNA: discovery, characterization, and clinical utility for oral cancer detection[J]. Clin Cancer Res, 2009, 15(17): 5473-5477.
[18] CHEN X, BA Y, MA L, et al. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases[J]. Cell Res, 2008, 18(10): 997-1006.
[19] ZHENG D, HADDADIN S, WANG Y, et al. Plasma microRNAs as novel biomarkers for early detection of lung cancer[J]. Int J Clin Exp Pathol, 2011, 4(6): 575-586.
[20] PERFETTI A, GRECO S, BUGIARDINI E, et al. Plasma microRNAs as biomarkers for myotonic dystrophy type 1[J].Neuromuscul Disord, 2014, 24(6): 509-515.
[21] KJERSEM J B, IKDAHL T, LINGJAERDE O C, et al. Plasma microRNAs predicting clinical outcome in metastatic colorectal cancer patients receiving first-line oxaliplatinbased treatment[J]. Mol Oncol, 2014, 8(1): 59-67.
[22] ZHANG W, SHANG T, HUANG C, et al. Plasma microRNAs serve as potential biomarkers for abdominal aortic aneurysm[J]. Clin Biochem, 2015, 48(15): 988-992.
[23] PENG P, LI Z, LIU X. Reduced Expression of miR-23a Suppresses A20 in TLR-stimulated Macrophages[J]. Inflammation, 2015, 38(5): 1787-1793.
[24] SARRION I, MILIAN L, JUAN G, et al. Role of circulating miRNAs as biomarkers in idiopathic pulmonary arterial hypertension: possible relevance of miR-23a[J]. Oxid Med Cell Longev, 2015, 2015: 792846.
[25] CAI S, CHEN R, LI X, et al. Downregulation of microRNA-23a suppresses prostate cancer metastasis by targeting the PAK6-LIMK1 signaling pathway[J]. Oncotarget, 2015, 6(6):3904-3917.
[26] LIN R, SAMPSON J H, LI Q J, et al. miR-23a blockade enhances adoptive T cell transfer therapy by preserving immune-competence in the tumor microenvironment[J]. Oncoimmunology, 2015, 4(3): e990803.
[27] LUO Z, FENG X, WANG H, et al. Mir-23a induces telomere dysfunction and cellular senescence by inhibiting TRF2 expression[J]. Aging Cell, 2015, 14(3): 391-399.
[28] CORTEZ M A, CALIN G A. MicroRNA identification in plasma and serum: a new tool to diagnose and monitor diseases[J]. Expert Opin Biol Ther, 2009, 9(6): 703-711.
[29] SURYAWANSHI S, VLAD A M, LIN H M, et al. Plasma microRNAs as novel biomarkers for endometriosis and endometriosis-associated ovarian cancer[J]. Clin Cancer Res, 2013, 19(5): 1213-1224.