首页|长链非编码RNA结直肠肿瘤差异表达基因微RNA-181a-5p和自噬相关蛋白5在原发性痛风性关节炎中的表达及临床意义

长链非编码RNA结直肠肿瘤差异表达基因微RNA-181a-5p和自噬相关蛋白5在原发性痛风性关节炎中的表达及临床意义

Expression and clinical significance of long non-coding RNA differentially expressed genes,micro RNA-181a-5p and autophagy-related protein 5 in primary gouty arthritis

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目的 探索长链非编码RNA(lncRNA)结直肠肿瘤差异表达基因(CRNDE)、微RNA-181a-5p(miR-181a-5p)、自噬相关蛋白5(ATG5)在原发性痛风性关节炎(GA)患者外周血中的表达及临床意义.方法 收集80例GA患者[急性期痛风(AG)、间歇期痛风(IG)各40例]和50名健康体检者(HC)临床资料、实验室检查指标及外周血标本.采用实时荧光定量PCR(RT-qPCR)检测lncRNA CRNDE、miR-181a-5p、ATG5mRNA表达水平;蛋白质印迹法检测ATG5蛋白表达水平.比较3组间lncRNA CRNDE、miR-181a-5p、ATG5 mRNA表达量并与临床指标做相关性分析,构建受试者工作特征曲线(ROC)评估lncRNA CRNDE、miR-181a-5p、ATG5 mRNA在痛风诊断中的价值.符合正态分布的计量资料使用t检验或方差分析,非正态分布用Mann-Whitney U检验或Kruskal-Wallis H检验,变量间的相关分析采用Spearman分析,各指标的诊断价值采用ROC曲线.结果 ①LncRNA CRNDE、miR-181a-5p、ATG5 mRNA在3组间表达差异均有统计学意义(H=32.12、57.73、68.32,P均<0.001).其中,lncRNA CRNDE表达水平在AG组明显高于 IG 组和健康对照组[61.95(11.39,108.30)×10-3,25.71(15.40,38.40)×10-3,13.80(3.97,23.99)×10-3;Z=-3.24,P=0.001;Z=-5.03,P<0.001],且在 IG 组的表达水平高于健康对照组(Z=-3.56,P<0.001);miR-181a-5p、ATG5mRNA表达水平在AG组明显低于IG组及健康对照组[miR-181a-5p:39.81(31.22,69.38)× 10-3,60.74(44.19,90.35)×10-3,121.30(101.50,316.90)×10-3;Z=-3.01,P=0.030;Z=-6.93,P<0.001.ATG5 mRNA:4.52(2.31,26.63)x10-3,43.63(13.72,102.70)x10-3,153.90(66.62,365.80)×10-3;Z=-5.47、-7.36,P均<0.001)],在IG组的表达水平低于健康对照组(Z=-5.25、-4.47,P均<0.001).ATG5蛋白表达水平在3组间表达的差异有统计学意义(F=6.24,P=0.030),AG组高于健康对照组,差异有统计学意义[(0.96±0.13)与(0.61±0.04),t=4.25,P=0.013],但 IG 组(0.78±0.15)与 AG组(t=1.51,P=0.206)、HC 组(t=1.85,P=0.138)差异无统计学意义.②Spearman相关性分析显示,在GA组中lncRNA CRNDE与miR-181a-5p、ATG5 mRNA 的表达水平呈负相关(r=-0.49,P<0.001;r=-0.35,P=0.002);miR-181 a-5p 与 ATG5 mRNA表达水平在呈正相关(r=0.64,P<0.001);lncRNA CRNDE表达水平与ESR、WBC呈正相关(r=0.49,P<0.001;r=0.43,P=0.001);miR-181 a-5p 表达水平与 ESR、WBC 呈负相关(r=-0.29,P=0.009;r=-0.35,P=0.002);ATG5 mRNA 表达水平与 ESR、WBC、中性粒细胞绝对值(GR)呈负相关(r=-0.26,P=0.021;r=-0.26,P=0.024;r=-0.27,P=0.021).在 AG 组中 lncRNA CRNDE 与 ESR、WBC 呈正相关(r=0.36,P=0.022;r=0.36,P=0.026),miR-181a-5p 与 WBC 呈负相关(t=-0.34,P=0.038).③ROC 曲线显示:lncRNA CRNDE、miR-181a-5p、ATG5 mRNA表达水平预测痛风的ROC曲线下面积分别为0.764、0.875、0.864;三者联合预测痛风的ROC曲线下面积为0.928.结论 LncRNA CRNDE、miR-181a-5p、ATG5可能参与了 GA的发病机制,并且有望成为监测痛风发病的生物学指标.
Objective To explore the expression and clinical significance of long non-coding RNA colorectal neoplasia differentially expressed(lncRNA CRNDE),microRNA-181a-5p(miR-181a-5p)and autophagy related 5(ATG5)in the peripheral blood of patients with gouty arthritis(GA)patients.Methods The clinical data,laboratory parameters and peripheral blood samples were collected from 40 patients with acute gout(AG),40 patients with intermittent gout(IG)and 50 healthy subjects(HC).The expression levels of lncRNA CRNDE,miR-181a-5p and ATG5 mRNA were detected by real-time fluorescence quantification(RT-qPCR)and the expression level of ATG5 protein was detected by Western-blot.The expression levels of lncRNA CRNDE,miR-181a-5p,ATG5 mRNA were compared among the three groups and correlated with clinical indices,and a subject operating characteristic curve(ROC)was constructed to assess the value of lncRNA CRNDE,miR-181a-5p,ATG5 mRNA in the diagnosis of gout.Measurements conforming to normal distribution were analyzed using t test or ANOVA,data with non-normal distribution was analyzed using Mann-Whitney U test or Kruskal-Wallis H test,correlation analysis between variables was analyzed using Spearman's analysis,and the diagnostic value of each indicator was analyzed using ROC curve.Results ① The differences in the expression of lncRNA CRNDE,miR-181a-5p,and ATG5 mRNA between the three groups were statistically significant(H=32.12,57.73,68.32,all P<0.001).Among them,lncRNA CRNDE expression level in the AG group was significantly higher than that in the IG group and healthy control group[61.95(11.39,108.30)×10-3,25.71(15.40,38.40)×10-3,13.80(3.97,23.99)×10-3;Z=-3.24,P=0.001;Z=-5.03,P<0.001],and the expression level of IG group was higher than that of healthy control group(Z=-3.56,P<0.001);miR-181a-5p and ATG5 mRNA expression levels in AG group were significantly lower than those in IG group and healthy control group[miR-181a-5p:39.81(31.22,69.38)×10-3,60.74(44.19,90.35)×10-3,121.30(101.50,316.90)×10-3;Z=-3.01,P=0.030;Z=-6.93,P<0.001.ATG5 mRNA:4.52(2.31,26.63)×10-3,43.63(13.72,102.70)×10-3,153.90(66.62,365.80)×10-3;Z=-5.47,-7.36,all P<0.001)],which were expressed at lower levels in the IG group than in the healthy controls(Z=-5.25,-4.47,all P<0.001).The difference of ATG5 protein expression level among the three groups expressed was statistically significant(F=6.24,P=0.030),and the AG group was higher than the healthy control group,and the difference was statistically significant[(0.96±0.13)vs.(0.61±0.04),t=4.25,P=0.013],but the difference between the IG group(0.78±0.15)and the AG group and the HC group was not statistically significant(t=1.51,P=0.206;t=1.85,P=0138).② Spearman correlation analysis showed that lncRNA CRNDE was negatively correlated with the expression levels of miR-181a-5p and ATG5 mRNA in gout patients(r=-0.49,P<0.001;r=-0.35,P=0.002);miR-181a-5p was positively correlated with ATG5 mRNA expression levels(r=0.64,P<0.001);lncRNA CRNDE expression level was positively correlated with ESR and WBC(r=0.49,P<0.001;r=0.43,P=0.001);miR-181a-5p expression level was negatively correlated with ESR and WBC(r=-0.29,P=0.009;r=-0.35,P=0.002),and ATG5 mRNA expression levels were negatively correlated with ESR,WBC,and GR(r=-0.26,P=0.021;r=-0.26,P=0.024;r=-0.27,P=0.021).In the AG group lncRNA CRNDE was positively correlated with ESR and WBC(r=0.36,P=0.022;r=0.36,P=0.026)and miR-181a-5p was negatively correlated with WBC(r=-0.34,P=0.038)③ ROC curve showed that the areas under ROC curve of lncRNA CRNDE,miR-181a-5p and ATG5 mRNA expression levels to predict gout were 0.764,0.875 and 0.864,respectively.The area under ROC curve of gout predicted by the three combined was 0.928.Conclusion lncRNA CRNDE,miR-181a-5p,and ATG5 may be involved in the pathoge-nesis of primary gouty arthritis,and are potential biological parameters for studying the pathogenesis of gout.

Arthritis,goutyRNA,long noncodingMicroRNAsAutophagy-related protein 5

郭建伟、雷天意、王鹏、张曾、简桂林、张全波、青玉凤

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川北医学院附属医院高尿酸血症与痛风研究中心,南充 637000

川北医学院附属医院风湿免疫科,南充 637000

川北医学院附属医院老年科,南充 637000

遂宁市第三人民医院急诊科,遂宁 629000

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关节炎,痛风性 RNA,长链非编码 微RNAs 自噬相关蛋白5

国家自然科学基金面上项目四川省南充市科技计划四川省南充市科技计划川北医学院附属医院科研项目

8197425020SXQT030820SX-CXTD00022022ZD003

2024

中华风湿病学杂志
中华医学会

中华风湿病学杂志

CSTPCD
影响因子:0.651
ISSN:1007-7480
年,卷(期):2024.28(5)
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