miRNA-181a在系统性红斑狼疮患者血浆中的表达及临床意义
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摘要
目的研究mi RNA-181a检测在系统性红斑狼疮患者临床诊治中的价值。方法采用反转录PCR法(RT-PCR)检测36例2015年1~6月来我院门诊和住院就诊的系统性红斑狼疮(SLE)患者及30例同期来我院健康体检的对照者的血浆mi RNA-181a相对表达量,同时测定SLE患者的血沉(ESR)、C反应蛋白(CRP)与免疫球蛋白Ig G、IgA、IgM和补体C3、C4及系统性红斑狼疮活动指数(SLEDAI)等,分析miRNA-181a与这些临床指标的关系。结果SLE组miRNA-181a相对表达水平显著高于健康对照组,SLE活动期组高于SLE稳定期组,差异均有统计学意义(P<0.05)。SLE患者血浆mi RNA-181a相对表达水平与血沉、C反应蛋白、SLEDAI评分等呈正相关(r=0.48、0.56、0.62,P均<0.05)。结论血浆mi RNA-181a浓度在SLE患者体内明显升高,且与SLE患者目前常用的一些临床评估指标高度相关,mi RNA-181a有可能成为一个新的SLE疾病活动度评估及预后判断的分子标志物。
Objective To study the value of miRNA-181 a detection in the diagnosis and treatment of systemic lupus erythematosus(SLE) patients. Methods RT-PCR method was used to detect relative expression of mi RNA-181 a in plasma of 36 outpatients and inpatients with systemic lupus erythematosus(SLE) in our hospital from Jan. to Jun. 2015; and30 health examination persons in the same period. At the same time, erythrocyte sedimentation rate(ESR), C-reactive protein(CRP), immunoglobulin Ig G, Ig A, Ig M and complement C3, C4, systemic lupus erythematosus disease activity index(SLEDAI) etc. were detected to analyze the relationship between miRNA-181 a and the clinical characteristics of SLE patients. Results The relative expression level of miRNA-181 a in SLE group was significantly higher than that in healthy control group, SLE active phase group was higher than that of SLE stable phase group, and the differences were statistically significant(P<0.05). The relative expression level of mi RNA-181 a in plasma of SLE patients was positively related with ESR, CRP and SLEDAI scores etc.(r=0.48, 0.56, 0.62, P all<0.05). Conclusion The concentration of plasma miRNA-181 a significantly increases in SLE patients, which is highly correlated with SLE patients present clinical evaluation indicators, mi RNA-181 a may be used as a symbol of a new assessment of SLE disease activity and prognosis.
Objective To study the value of miRNA-181 a detection in the diagnosis and treatment of systemic lupus erythematosus(SLE) patients. Methods RT-PCR method was used to detect relative expression of mi RNA-181 a in plasma of 36 outpatients and inpatients with systemic lupus erythematosus(SLE) in our hospital from Jan. to Jun. 2015; and30 health examination persons in the same period. At the same time, erythrocyte sedimentation rate(ESR), C-reactive protein(CRP), immunoglobulin Ig G, Ig A, Ig M and complement C3, C4, systemic lupus erythematosus disease activity index(SLEDAI) etc. were detected to analyze the relationship between miRNA-181 a and the clinical characteristics of SLE patients. Results The relative expression level of miRNA-181 a in SLE group was significantly higher than that in healthy control group, SLE active phase group was higher than that of SLE stable phase group, and the differences were statistically significant(P<0.05). The relative expression level of mi RNA-181 a in plasma of SLE patients was positively related with ESR, CRP and SLEDAI scores etc.(r=0.48, 0.56, 0.62, P all<0.05). Conclusion The concentration of plasma miRNA-181 a significantly increases in SLE patients, which is highly correlated with SLE patients present clinical evaluation indicators, mi RNA-181 a may be used as a symbol of a new assessment of SLE disease activity and prognosis.
引文
[1]Shen N,Liang D,Tang Y,et al.Micro RNAs-novel regulators of systemic lupus erythematosus pathogenesis[J].Na ture reviews Rheumatology,2012,8(12):701-709.
[2]Gladman DD,Iblanez D,Urowitz MB.Systemic lupus erythematosus disease activity index 2000[J].Rheumatol,2002,29(2):288.
[3]Livak KJ,Schmittgen TD.Analysis of relative gene expression data using real-time quantitative PCR and the 2[-Delta Delta C(T)]Method[J].Methods,2001,25(4):402-408.
[4]Zietara N,Lyszkiewicz M,Witzlau K,et al.Critical role for mi R-181a/b-1 in agonist selection of invariant natural killer T cells[J].Proceedings of the National Academy of Sciences USA,2013,110(18):7407-7412.
[5]Ji J,Yamashita T,Budhu A,et al.Identification of micro RNA-181 by genome-wide screening as a critical player in Ep CAM-positive hepatic cancer stem cells[J].Hepatology,2009,50(2):472-480.
[6]Fragoso R,Mao T,Wang S,et al.Modulating the strength and threshold of NOTCH oncogenic signals by mir-181a-1/b-1[J].PLo S Genetics,2012,8(8):e1002855.
[7]Zou C,Chen J,Chen k,et al.Functional analysis of mi R-181a and Fas involved in hepatitis B virus-related hepatocellular carcinoma pathogenesis[J].Exp Cell Res,2015,331(2):352-361.
[8]Wei Z,Cui l,Mei Z,et al.mi RNA-181a mediates metabolic shift in colon cancer cells via the PTEN/AKT pathway[J].FEBS Lett,2014,588(9):1773-1779.
[9]Lashine YA,Seoudi AM,Salah S,et al.Expression signature of micro RNA-181a reveals its crucial role in the pathogenesis of paediatric systemic lupus erythematosus[J].Clin Exp Rheumatol,2011,29(2):351-357.
[10]Tsokos GC.Systemic lupus erythematosus[J].New Eng land Journal of Medicine,2011,365(22):2110-2121.
[11]Yang J,Lu YW,Lu MM,et al.Microma-101,mitogenactivated protein kinases and mitogen-activated protein kinases phospha-tase-1 in systemic lupus erythematosus[J].Lupus,2013,22(2):115-120.
[12]Shen N,Liang D,Tang Y,et al.Micro RNAs-novel regulators of systemic lupus erythematosus pathogenesis[J].Nature Reviews Rheumatology,2012,8(12):701-709.
[13]Carlsen AL,Schetter AJ,Nielsen CT,et al.Circulating micro RNA expression profiles associated with systemic lupus erythematosus[J].Arthritis&Rheumatology,2013,65(5):1324-1334.
[14]Motawi TK,Mohsen DA,El-Maraghy SA,et al.Micro RNA-21,micro RNA-181a and micro RNA-196a as potential biomarkers in adult Egyptian patients with systemic lupus erythematosus[J].Chem Biol Interact,2016,260:110-116.
[15]Stypinska B,Paradowska-Gorycka A.Cytokines and micro RNAs as candidate biomarkers for systemic lupus erythematosus[J].Int J Mol Sci,2015,16(10):24194-24218.
[16]Galicia JC,Naqvi AR,Ko CC,et al.mi RNA-181a regulates Toll like receptor agonist-induced inflammatory response in human fibroblasts[J].Genes and Immunity,2014,15(5):333-337.
[17]Xie W,Li Z,Li M,et al.Mi R-181a and inflammation:mi RNA homeostasis response to inflammatory stimuli in vivo[J].Biochemical and Biophysical Research Communications,2013,430(2):647-652.
[18]Mina R,Brunner HI.Update on differences between childhood-onset and adult-onset systemic lupus erythematosus[J].Arthritis Res Ther,2013,15(4):218.
[19]Choi JH,Park DJ,Kang JH,et al.Comparison of clinical and serological differences among juvenile-,adult-,and late-onset systemic lupus erythematosus in Korean patients[J].Lupus,2015,24(12)1342-1349.
[20]Aggarwal A,Srivastava P.Childhood onset systemic lupus erythematosus:How is it different from adult SLE?[J].Int J Rheum Dis,2015,18(2):182-191.
[2]Gladman DD,Iblanez D,Urowitz MB.Systemic lupus erythematosus disease activity index 2000[J].Rheumatol,2002,29(2):288.
[3]Livak KJ,Schmittgen TD.Analysis of relative gene expression data using real-time quantitative PCR and the 2[-Delta Delta C(T)]Method[J].Methods,2001,25(4):402-408.
[4]Zietara N,Lyszkiewicz M,Witzlau K,et al.Critical role for mi R-181a/b-1 in agonist selection of invariant natural killer T cells[J].Proceedings of the National Academy of Sciences USA,2013,110(18):7407-7412.
[5]Ji J,Yamashita T,Budhu A,et al.Identification of micro RNA-181 by genome-wide screening as a critical player in Ep CAM-positive hepatic cancer stem cells[J].Hepatology,2009,50(2):472-480.
[6]Fragoso R,Mao T,Wang S,et al.Modulating the strength and threshold of NOTCH oncogenic signals by mir-181a-1/b-1[J].PLo S Genetics,2012,8(8):e1002855.
[7]Zou C,Chen J,Chen k,et al.Functional analysis of mi R-181a and Fas involved in hepatitis B virus-related hepatocellular carcinoma pathogenesis[J].Exp Cell Res,2015,331(2):352-361.
[8]Wei Z,Cui l,Mei Z,et al.mi RNA-181a mediates metabolic shift in colon cancer cells via the PTEN/AKT pathway[J].FEBS Lett,2014,588(9):1773-1779.
[9]Lashine YA,Seoudi AM,Salah S,et al.Expression signature of micro RNA-181a reveals its crucial role in the pathogenesis of paediatric systemic lupus erythematosus[J].Clin Exp Rheumatol,2011,29(2):351-357.
[10]Tsokos GC.Systemic lupus erythematosus[J].New Eng land Journal of Medicine,2011,365(22):2110-2121.
[11]Yang J,Lu YW,Lu MM,et al.Microma-101,mitogenactivated protein kinases and mitogen-activated protein kinases phospha-tase-1 in systemic lupus erythematosus[J].Lupus,2013,22(2):115-120.
[12]Shen N,Liang D,Tang Y,et al.Micro RNAs-novel regulators of systemic lupus erythematosus pathogenesis[J].Nature Reviews Rheumatology,2012,8(12):701-709.
[13]Carlsen AL,Schetter AJ,Nielsen CT,et al.Circulating micro RNA expression profiles associated with systemic lupus erythematosus[J].Arthritis&Rheumatology,2013,65(5):1324-1334.
[14]Motawi TK,Mohsen DA,El-Maraghy SA,et al.Micro RNA-21,micro RNA-181a and micro RNA-196a as potential biomarkers in adult Egyptian patients with systemic lupus erythematosus[J].Chem Biol Interact,2016,260:110-116.
[15]Stypinska B,Paradowska-Gorycka A.Cytokines and micro RNAs as candidate biomarkers for systemic lupus erythematosus[J].Int J Mol Sci,2015,16(10):24194-24218.
[16]Galicia JC,Naqvi AR,Ko CC,et al.mi RNA-181a regulates Toll like receptor agonist-induced inflammatory response in human fibroblasts[J].Genes and Immunity,2014,15(5):333-337.
[17]Xie W,Li Z,Li M,et al.Mi R-181a and inflammation:mi RNA homeostasis response to inflammatory stimuli in vivo[J].Biochemical and Biophysical Research Communications,2013,430(2):647-652.
[18]Mina R,Brunner HI.Update on differences between childhood-onset and adult-onset systemic lupus erythematosus[J].Arthritis Res Ther,2013,15(4):218.
[19]Choi JH,Park DJ,Kang JH,et al.Comparison of clinical and serological differences among juvenile-,adult-,and late-onset systemic lupus erythematosus in Korean patients[J].Lupus,2015,24(12)1342-1349.
[20]Aggarwal A,Srivastava P.Childhood onset systemic lupus erythematosus:How is it different from adult SLE?[J].Int J Rheum Dis,2015,18(2):182-191.