非小细胞肺癌患者血清外泌体中miR-539的临床意义及生物学功能研究  

Clinical significance and biological function of miR-539 in serum exosomes of patients with non-small cell lung cancer

作　　者：梁月兰[1] 王进[2] 李建祥[2] LIANG Yuelan;WANG Jin;LI Jianxiang(Suzhou Wuzhong People's Hospital,Jiangsu Suzhou 215100,China;School of Public Health,Suzhou Medical College of Soochow University,Jiangsu Suzhou 215123,China)

机构地区：[1]苏州市吴中人民医院,江苏苏州215100 [2]苏州大学苏州医学院公共卫生学院,江苏苏州215123

出　　处：《现代肿瘤医学》2023年第17期3197-3204,共8页Journal of Modern Oncology

摘　　要：目的:分析非小细胞肺癌患者预后相关的外泌体miRNA的临床意义,并通过实验验证其功能,作为肺癌诊断和治疗的生物标志物。方法:从公共数据库下载非小细胞肺癌患者血清外泌体和肺癌组织的miRNA表达谱及临床数据;分别利用R语言“limma”“survival”和“survminer”包进行miRNA的差异表达分析和生存分析;通过靶基因富集分析预测miRNA生物学功能并分析其与免疫细胞浸润的相关性;在两种肺癌细胞中敲低miRNA,通过CCK-8、EdU和Transwell实验分析其对细胞增殖和迁移的影响;收集过表达miRNA肺癌细胞的外泌体,处理人正常支气管上皮细胞BEAS-2B并分析生物学功能变化。结果:基于差异分析和单因素COX分析,选定has-miR-539-5p(miR-539)进一步探究其与多个肿瘤相关信号通路和免疫系统相关;相关性分析表明miR-539表达与多种免疫细胞浸润显著相关;敲低miR-539能够显著降低肺癌细胞增殖和迁移能力,而过表达miR-539肺癌细胞外泌体处理正常肺细胞能够使其获得恶性细胞特征,包括增殖和迁移能力的增强。结论:miR-539能够调控肺癌细胞增殖和迁移能力,并且在非小细胞肺癌患者肿瘤组织和血清外泌体中上调,对患者诊断和预后具有重要的指导意义。Objective:To analyze the clinical significance of prognosis related exocrine miRNA in patients with non-small cell lung cancer(NSCLC),and verify their functions through experiments as biomarkers for the diagnosis and treatment of lung cancer.Methods:The miRNA expression profiles and clinical data of serum exosomes and lung cancer tissues of NSCLC patients were downloaded from the public database.The differential expression analysis and survival analysis of miRNA was carried out using R language"limma""survival"and"survminer"packages respectively.The biological function of miRNA was predicted by target gene enrichment analysis and its correlation with immune cell infiltration was analyzed.Knock down miRNA in two kinds of lung cancer cells,and analyze their effects on cell proliferation and migration through CCK-8,EdU and Transwell experiments.The exosomes of miRNA overexpressing lung cancer cells were collected and treated with human normal bronchial epithelial cells BEAS-2B,and the changes of biological functions were analyzed.Results:Based on differential analysis and single factor COX analysis,has-miR-539-5p(miR-539)was selected for further exploration,which was related to multiple tumor related signal pathways and immune system.Correlation analysis showed that miR-539 expression was significantly correlated with multiple immune cell infiltration.Knocking down miR-539 can significantly reduce the proliferation and migration of lung cancer cells,while treating normal lung cells from the secretions of overexpressing miR-539 lung cancer cells can enable them to obtain malignant cell characteristics,including enhanced proliferation and migration.Conclusion:miR-539 can regulate the proliferation and migration of lung cancer cells,and it is up-regulated in tumor tissues and serum secretions of non-small cell lung cancer patients,which has important guiding significance for the diagnosis and prognosis of patients.

关 键 词：非小细胞肺癌 外泌体 miR-539 预后 增殖 迁移 

分 类 号：R734.2[医药卫生—肿瘤]