系统性红斑狼疮患者外周血miR-21、miR-148a和miR-196a的表达分析
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摘要
目的探讨miR-21、miR-148a、miR-196a在系统性红斑狼疮(SLE)患者外周血血浆、单个核细胞(PBMC)的表达水平,为研究miRNAs在SLE发病机制中的调控作用和临床诊断价值提供新的思路。方法收集SLE患者及正常人外周血,分离血浆及PBMC,RT-PCR检测miR-21、miR-148a、miR-196a的表达量,ROC曲线评价其对SLE诊断的敏感度及特异度。结果 SLE患者外周血血浆及PBMC中miR-21、miR-148a的表达水平升高,miR-196a的表达降低(P<0.01)。ROC曲线分析表明,血浆及PBMC中miR-21、miR-148a、miR-196a对SLE具有较高的诊断敏感度及特异度。结论 SLE患者外周血中miR-21、miR-148a、miR-196a表达量存在差异,这种差异对SLE具有较强的临床诊断能力,有望成为新的临床诊断标志物。
Objective To investigate the expression levels of miR-21, miR-148 a and miR-196 a in peripheral blood plasma and mononuclear cells(PBMC) of patients with systemic lupus erythematosus(SLE), so as to provide new ideas for studying the regulatory role and clinical diagnostic value of miRNAs in the pathogenesis of SLE. Methods Peripheral blood of SLE patients and normal subjects were collected, plasma and PBMC were isolated, and the expression levels of miR-21, miR-148 a and miR-196 a were detected by RT-PCR. The sensitivity and specificity of SLE diagnosis were evaluated by ROC curve. Results The expressions of miR-21 and miR-148 a in peripheral blood and PBMC of SLE patients significantly increased, and the expression of miR-196 a significantly decreased(P<0.01). ROC curve analysis showed that miR-21, miR-148 a and miR-196 a in plasma and PBMC had high diagnostic sensitivity and specificity to SLE. Conclusion The expressions of miR-21, miR-148 a and miR-196 a in peripheral blood of SLE patients are different. This difference has a strong clinical diagnostic ability to SLE, and it is expected to be a new clinical diagnostic marker.
Objective To investigate the expression levels of miR-21, miR-148 a and miR-196 a in peripheral blood plasma and mononuclear cells(PBMC) of patients with systemic lupus erythematosus(SLE), so as to provide new ideas for studying the regulatory role and clinical diagnostic value of miRNAs in the pathogenesis of SLE. Methods Peripheral blood of SLE patients and normal subjects were collected, plasma and PBMC were isolated, and the expression levels of miR-21, miR-148 a and miR-196 a were detected by RT-PCR. The sensitivity and specificity of SLE diagnosis were evaluated by ROC curve. Results The expressions of miR-21 and miR-148 a in peripheral blood and PBMC of SLE patients significantly increased, and the expression of miR-196 a significantly decreased(P<0.01). ROC curve analysis showed that miR-21, miR-148 a and miR-196 a in plasma and PBMC had high diagnostic sensitivity and specificity to SLE. Conclusion The expressions of miR-21, miR-148 a and miR-196 a in peripheral blood of SLE patients are different. This difference has a strong clinical diagnostic ability to SLE, and it is expected to be a new clinical diagnostic marker.
引文
[1] 陈玲玲, 孙学慧, 王海龙, 等. 系统性红斑狼疮患者自身抗体分析[J]. 中国卫生检验杂志, 2015, 25(15):2637-2638.
[2] 李传静, 乐静, 刘爱林, 等. 系统性红斑狼疮患者血清IL-23 表达水平及临床相关性研究[J]. 临床和实验医学杂志, 2015, 14(3):204-207.
[3] 吴希国, 刘秀珍, 马越. 173例系统性红斑狼疮患者ANA、ENA和dsDNA抗体的联合检测分析[J]. 中国卫生检验杂志, 2012, 22(4): 781-782.
[4] 范薇, 唐元家, 曲波, 等. 系统性红斑狼疮患者外周血细胞miR-31的表达[J]. 上海交通大学学报: 医学版, 2011, 31(1):39-42.
[5] 郑锡铭, 刘鑫, 周林林, 等. 6种miRNAs在类风湿关节炎患者外周血及关节液中的表达分析[J]. 中国免疫学杂志, 2014(12):1686-1691.
[6] Li L, Chen XP, Li YJ. MicroRNA-146a and human disease[J]. Scand J Immunol, 2010, 71(4): 227-231.
[7] Stagakis E, Bertsias G, Verginis P, et al. Identification of novel microRNA signatures linked to human lupus disease activity and pathogenesis: miR-21 regulates aberrant T cell responses through regulation of PDCD4 expression[J]. Ann Rheum Dis, 2011, 70(8): 1496-1506.
[8] Zhao X, Tang Y, Qu B, et al. MicroRNA-125a contributes to elevated inflammatory chemokine RANTES levels via targeting KLF13 in systemic lupus erythematosus[J]. Arthritis Rheum, 2010, 62(11): 3425-3435.
[9] Lu MC, Lai NS, Chen HC, et al. Decreased microRNA(miR)-145and increased miR-224 expression in T cells from patients with systemic lupus erythematosus involved in lupus immunob pathogenesis[J]. Clin Exp Immunol, 2013, 1719(10): 91-99.
[10] Kurowska-Stolarska M, Alivernini S, Ballantine LE, et al. MicroRNA-155 as a proinflammatory regulator in clinical and experimental arthritis[J]. Proc Natl Acad Sci USA, 2011, 108: 11193-11198.
[11] Lofgren SE, Frostegard J, Edsson L, et al. Genetic association of miRNA-146 a with systemic lupus erythematosus in Europeans through decreased expression of the gene[J]. Genes Immun, 2012, 13: 268-274.
[12] 董利阳, 汪雪峰, 苏川. MicroRNA-21在自身免疫性疾病中的调节作用与机制[J]. 细胞与分子免疫学杂志, 2013, 29(9):993-996.
[13] Pan W, Zhu S, Yuan M, et al. MicroRNA-21 and microRNA148a contribute to DNA hypomethylation in lupus CD4~+Tcells by directly and indirectly targeting DNMT1[J]. J Immunol, 2010, 184: 6773-6781.
[14] 范薇, 沈南, 唐元家. MicroRNA参与系统性红斑狼疮发病机制的研究进展[J]. 现代免疫学, 2010, 30(4):346-349.
[15] 彭武建, 黄远帅, 张丽, 等. 系统性红斑狼疮患者外周血中差异表达微小RNAs的筛选[J]. 广东医学, 2012, 33(7):922-925.
[2] 李传静, 乐静, 刘爱林, 等. 系统性红斑狼疮患者血清IL-23 表达水平及临床相关性研究[J]. 临床和实验医学杂志, 2015, 14(3):204-207.
[3] 吴希国, 刘秀珍, 马越. 173例系统性红斑狼疮患者ANA、ENA和dsDNA抗体的联合检测分析[J]. 中国卫生检验杂志, 2012, 22(4): 781-782.
[4] 范薇, 唐元家, 曲波, 等. 系统性红斑狼疮患者外周血细胞miR-31的表达[J]. 上海交通大学学报: 医学版, 2011, 31(1):39-42.
[5] 郑锡铭, 刘鑫, 周林林, 等. 6种miRNAs在类风湿关节炎患者外周血及关节液中的表达分析[J]. 中国免疫学杂志, 2014(12):1686-1691.
[6] Li L, Chen XP, Li YJ. MicroRNA-146a and human disease[J]. Scand J Immunol, 2010, 71(4): 227-231.
[7] Stagakis E, Bertsias G, Verginis P, et al. Identification of novel microRNA signatures linked to human lupus disease activity and pathogenesis: miR-21 regulates aberrant T cell responses through regulation of PDCD4 expression[J]. Ann Rheum Dis, 2011, 70(8): 1496-1506.
[8] Zhao X, Tang Y, Qu B, et al. MicroRNA-125a contributes to elevated inflammatory chemokine RANTES levels via targeting KLF13 in systemic lupus erythematosus[J]. Arthritis Rheum, 2010, 62(11): 3425-3435.
[9] Lu MC, Lai NS, Chen HC, et al. Decreased microRNA(miR)-145and increased miR-224 expression in T cells from patients with systemic lupus erythematosus involved in lupus immunob pathogenesis[J]. Clin Exp Immunol, 2013, 1719(10): 91-99.
[10] Kurowska-Stolarska M, Alivernini S, Ballantine LE, et al. MicroRNA-155 as a proinflammatory regulator in clinical and experimental arthritis[J]. Proc Natl Acad Sci USA, 2011, 108: 11193-11198.
[11] Lofgren SE, Frostegard J, Edsson L, et al. Genetic association of miRNA-146 a with systemic lupus erythematosus in Europeans through decreased expression of the gene[J]. Genes Immun, 2012, 13: 268-274.
[12] 董利阳, 汪雪峰, 苏川. MicroRNA-21在自身免疫性疾病中的调节作用与机制[J]. 细胞与分子免疫学杂志, 2013, 29(9):993-996.
[13] Pan W, Zhu S, Yuan M, et al. MicroRNA-21 and microRNA148a contribute to DNA hypomethylation in lupus CD4~+Tcells by directly and indirectly targeting DNMT1[J]. J Immunol, 2010, 184: 6773-6781.
[14] 范薇, 沈南, 唐元家. MicroRNA参与系统性红斑狼疮发病机制的研究进展[J]. 现代免疫学, 2010, 30(4):346-349.
[15] 彭武建, 黄远帅, 张丽, 等. 系统性红斑狼疮患者外周血中差异表达微小RNAs的筛选[J]. 广东医学, 2012, 33(7):922-925.