CircPTPN22作为miR-766-3p分子海绵促进类风湿关节炎病理进程  

CircPTPN22 participates in RA by acting as a sponge for miR-766-3p

作　　者：唐隽 陈雪猛 贾钰莹 李时飞 蒋柱燕 TANG Jun;CHEN Xuemeng;JIA Yuying;LI Shifei;JIANG Zhuyan(Department of Dermatology,First Affiliated Hospital,University of Science and Technology of China,Hefei 230001,China;Department of Rheumatology,Southwest Hospital,Third Military Medical University,Chongqing 400038,China;Department of Dermatology,Clinical College of Anhui Medical University,Hefei 230001,China;Department of Dermatology,Southwest Hospital,Third Military Medical University,Chongqing 400038,China)

机构地区：[1]中国科学技术大学附属第一医院(安徽省立医院)皮肤科,合肥230001 [2]陆军军医大学第一附属医院(西南医院)中医与风湿免疫科,重庆400038 [3]安徽医科大学解放军临床学院皮肤科,合肥230001 [4]陆军军医大学第一附属医院(西南医院)皮肤科,重庆400038

出　　处：《免疫学杂志》2022年第12期1060-1066,1073,共8页Immunological Journal

基　　金：国家自然科学基金面上项目(82273516);安徽省重点研究与开发计划(202004j07020002)。

摘　　要：目的本研究旨在探索circPTPN22在类风湿关节炎(RA)外周血单个核细胞(PBMCs)中的表达及参与RA的机制。方法RT-PCR检测circPTPN22在20例RA和20例健康人(HCs)PBMCs中的表达,生物信息学预测能与其结合的microRNA(miRNA),并用功能学实验和双荧光素酶试验进行验证。检测miRNA在RA患者PBMCs中的表达并计算受试者工作特征曲线(ROC)评估miRNA在RA中的临床意义。结果CircPTPN22表达水平在RA PBMCs中显著降低。ROC分析提示circPTPN22是RA患者的潜在诊断生物标志物(AUC=0.7025),相关性分析结果显示cirPTPN22的表达与RA的SJC、anti-CCP呈负相关关系(SJC:r=-0.723;anti-CCP:r=-0.618)。MiR-766-3p在RA PBMCs中显著上调;ROC分析提示miR-766-3p的表达可以将RA患者与HCs区分开来(AUC=0.9125)。生物信息学分析、双荧光素酶试验和功能学实验显示circPTPN22能抑制miR-766-3p的表达,miR-766-3p通过调控下游靶基因SIRT5参与RA。结论CircPTPN22通过与miR-766-3p竞争性结合调控下游靶基因SIRT5参与RA的发生与发展,且circPTPN22是RA的潜在诊断生物标志物。This study was performed to detect the expression of circPTPN22 in peripheral blood mononuclear cells(PBMCs)of rheumatoid arthritis(RA)and the possible mechanism involved in RA.RT-PCR was used to detect the expression of circPTPN22 in PBMCs of 20 RA and 20 healthy controls(HCs).MiRNAs,which could bind to circPTPN22,were predicted by bioinformatics and verified by functional experiments and dual luciferase assays.The expression of miRNA in PBMCs of RA patients was detected and the receiver operating characteristic curve(ROC)was calculated to evaluate the clinical significance of miRNA in RA.Compared with HCs,the expression level of circPTPN22 was significantly decreased in RA PBMCs.ROC analysis suggested that circPTPN22 was a potential diagnostic biomarker for RA patients(AUC=0.9125).Correlation analysis showed the expression level of circPTPN22 was negatively associated with the SJC and anti-CCP of RA(SJC:r=-0.723;anti-CCP:r=-0.618).Compared with HCs,miR-766-3p was significantly upregulated in RA PBMCs.ROC analysis suggested that the expression of miR-766-3p could distinguish RA patients from HCs(AUC=0.9125).Bioinformatics analysis,dual luciferase reporter system and functional experiments confirmed that circPTPN22 could inhibit the expression of miR-766-3p,which was involved in RA by regulating the downstream target gene SIRT5.All data in this study suggest that circPTPN22 may participate in the pathological process of RA by competitivelybinding to miR-766-3p to regulate downstream target gene SIRT5,and circPTPN22 may be a potential diagnosticbiomarker of RA.

关 键 词：类风湿关节炎 circPTPN22 miR-766-3p SIRT5 

分 类 号：R593.22[医药卫生—内科学]