Hsa-miR-155-3p和hsa-miR-155-5p作为系统性硬化症生物标志物及调控生物学行为的研究

Research on hsa-miR-155-3p and hsa-miR-155-5p as biomarkers for systemic sclerosis and their role in regulating biological behavior

目的:探讨hsa-miR-155-3p和hsa-miR-155-5p作为系统性硬化症(systemic sclerosis,SSc)生物标志物及调控生物学行为的研究。方法:选取10例SSc患者和10例健康对照者作为研究对象,采用RT-qPCR法检测SSc患者及健康对照者外周血单个核细胞(PBMCs)中hsa-miR-155-3p和hsa-miR-155-5p表达水平。应用受试者工作特征(ROC)曲线探究其诊断价值。Pearson或Spearman分析miRNA和SSc患者临床指标的相关性。利用miRDB、Targetscan和miRDIP数据库预测hsa-miR-155-3p和hsa-miR-155-5p靶基因,并进行GO功能注释和KEGG Pathway富集分析、PPI相互作用网络构建、中心基因的筛选。结果:在SSc患者PBMCs中hsa-miR-155-3p和hsa-miR-155-5p的表达水平均明显高于健康对照者(P<0.001)。ROC曲线显示,hsa-miR-155-3p和hsa-miR-155-5p诊断SSc的曲线下面积为(AUC=1, P<0.001)。相关性分析显示,hsa-miR-155-3p、 hsa-miR-155-5p和高分辨率CT(HRCT)、中性粒细胞百分比(NEUT%)、淋巴细胞百分比(LYM%)、白球比(ALB/GLB)等临床指标相关(P<0.05)。hsa-miR-155-3p和hsa-miR-155-5p靶基因富集的信号通路与SSc纤维化、免疫、炎症的发生发展密切相关。结论:hsa-miR-155-3p及hsa-miR-155-5p可能参与了调节SSc纤维化、免疫、炎症的发生、发展,hsa-miR-155-3p及hsa-miR-155-5p有可能作为SSc临床诊断和治疗的潜在生物标志物。

Objective:This study was to investigate the role of hsa-miR-155-3p and hsa-miR-155-5p as biomarkers and regulators of biological behavior in systemic sclerosis(SSc).Methods:A total of 10 SSc patients and 10 healthy controls were selected for the study.The expression levels of hsa-miR-155-3p and hsa-miR-155-5p in peripheral blood mononuclear cells of SSc patients and healthy controls were measured using RT-qPCR.The diagnostic value of these miRNAs was explored using Receiver Operating Characteristic curve analysis.Pearson or Spearman correlation analysis was performed to assess the correlation between miR-NAs and clinical indicators in SSc patients.Potential target genes of hsa-miR-155-3p and hsa-miR-155-5p were predicted using miRDB,Targetscan,and miRDIP databases.GO functional annotation,KEGG pathway enrichment analysis,protein-protein interaction network construction,and selection of central genes were conducted.Results:The expression levels of hsa-miR-155-3p and hsa-miR-155-5p were significantly higher in PBMCs of SSc patients compared to healthy controls(P<0.001).The ROC curve analysis showed that hsa-miR-155-3p and hsa-miR-155-5p had a high diagnostic value for SSc(AUC=1,P<0.001).Correlation analysis revealed that hsa-miR-155-3p,hsa-miR-155-5p,and clinical indicators such as high-resolution CT,neutrophil percentage,lymphocyte percentage,and albumin to globulin ratio were correlated(P<0.05).The signaling pathways enriched with target genes of hsa-miR-155-3p and hsa-miR-155-5p were closely associated with the occurrence and development of SSc fibrosis,immunity,and inflammation.Conclusions:Hsa-miR-155-3p and hsa-miR-155-5p may be involved in regulating the occurrence and development of SSc fibrosis,immunity,and inflammation.They have the potential to serve as biomarkers for clinical diagnosis and treatment of SSc.