膀胱癌患者尿液外泌体中miRNA差异表达谱及其生物信息学分析  

Differential expression profile and bioinformatic analysis of urine exosomal miRNA in bladder cancer patients

作　　者：邓益森 何宇辉[1,2] 应文伟 刘海龙 李沛哲 周晓峰 DENG Yisen;HE Yuhui;YING Wenwei;LIU Hailong;LI Peizhe;ZHOU Xiaofeng(Department of Urology,China-Japan Friendship Hospital,Beijing 100029,China;Peking University China-Japan Friendship School of Clinical Medicine,Beijing 100029,China)

机构地区：[1]中日友好医院泌尿外科,北京100029 [2]北京大学中日友好临床医学院,北京100029

出　　处：《现代肿瘤医学》2021年第3期446-450,共5页Journal of Modern Oncology

基　　金：国家自然科学基金(编号:81972403);国家国际科技合作专项(编号:2014DFE30010)。

摘　　要：目的:通过检测及筛选膀胱癌患者及正常人尿液外泌体中差异性表达的miRNA,进行生物学分析,探讨miRNA在膀胱癌发病中的作用。方法:利用超高速离心法及Illumina高通量测序技术分离并检测5例膀胱癌患者及5例配对正常人尿液标本中外泌体miRNA的表达情况,构建其差异表达谱。对差异表达基因进行生物信息学分析,确定差异表达miRNA的主要生物学功能及其可能参与的信号通路。结果:与正常人相比,膀胱癌患者尿液外泌体中共有38个miRNA显著异常表达,其中上调34个,下调4个。通过GO富集及KEGG分析,上述差异表达的miRNA可能通过趋化因子信号通路、PI3K-Akt信号通路、MAPK信号通路及RAS信号通路等参与膀胱癌的发生和发展过程,分别涉及脂质代谢、多糖降解、RNA降解及碱基切除修复等多种生化代谢途径,并参与细胞的粘连、内吞作用、突触囊泡循环等生物学过程。结论:膀胱癌患者尿液外泌体中miRNA的表达谱发生了显著的变化,has-miR-486-5p、 hsa-miR-199b-5p、hsa-miR-7704和has-miR-184等miRNA可能通过趋化因子信号通路、PI3K-Akt信号通路、MAPK信号通路及RAS信号通路等在膀胱癌的发生发展过程中发挥重要作用。Objective:To detect and screen differentially expressed miRNAs in urine exosomes of bladder cancer patients and normal humans,and to investigate the role of miRNAs in the pathogenesis of bladder cancer.Methods:Ultracentrifugation and Illumina high-throughput sequencing were used to separate and detect the expression of exosomal miRNA in urine samples from 5 bladder cancer patients and 5 matched individuals,and to construct differential expression profiles.Bioinformatic analysis was done to find the major biological functions of differentially expressed microRNAs and their possible signaling pathways.Results:Compared with normal subjects,there were 38 significantly differentially expressed miRNAs in urine exosomes of patients with bladder cancer,of which 34 were up-regulated and 4 were down-regulated.Through GO(Gene Ontology)enrichment and KEGG(Kyoto Encyclopedia of Genes and Genomes)analysis,the miRNAs may participate in the progression of bladder cancer through chemokine signaling pathway,PI3K-Akt signaling pathway,MAPK signaling pathway and RAS signaling pathway.Besides,they involved in lipid metabolism,polysaccharides degradation,RNA degradation and base excision repair and other biochemical metabolic pathways,and participated in a variety of biological processes such as cell adhesion,endocytosis and synaptic vesicle circulation.Conclusion:The expression profile of miRNA in urinary exosomes of bladder cancer patients has changed ramarkably.miRNAs such as has-miR-486-5p,hsa-miR-199b-5p,hsa-miR-7704 and has-miR-184 may play an important role in the development and progression of bladder cancer through chemokine signaling pathway,PI3K-Akt signaling pathway,MAPK signaling pathway and RAS signaling pathway.

关 键 词：膀胱癌 尿液 外泌体 MIRNA 生物信息学分析 

分 类 号：R737.14[医药卫生—肿瘤]