长链非编码RNA TUG1在肝细胞癌中的生物信息学分析  

Bioinformatics Analysis of long non-coding RNA TUG1 in hepatocellular carcinoma

作　　者：朱玉翠[1,2] 张晓彤 周亚男 胡成进 曹源[2] ZHU Yucui;ZHANG Xiaotong;ZHOU Yanan;HU Chengjin;CAO Yuan(Department of Medical Laboratory ,Weifang Medical University ,Weifang, Shandong 261053, China;Department of Clinical Laboratory ,General Hospital of JiZnan Command ,JiZnan ,Shandong 250031 ,China)

机构地区：[1]潍坊医学院医学检验学系,山东潍坊261053 [2]济南军区总医院实验诊断科,山东济南250031

出　　处：《国际检验医学杂志》2018年第10期1153-1157,1162,共7页International Journal of Laboratory Medicine

基　　金：国家自然科学基金资助项目(81472497;81572620);山东省自然科学基金资助项目(ZR2015HM003)

摘　　要：目的探讨长链非编码RNA(lncRNA)牛磺酸上调基因1(TUG1)在肝细胞癌(HCC)中的意义,并对TUG1进行靶基因预测,为TUG1在HCC中的进一步研究提供借鉴。方法利用UALCAN数据库分析TUG1在HCC中的差异表达,并对TUG1进行生存分析。利用RegRNA 2.0生物学软件、HMDD、targetscan、microT-CDS进行TUG1的靶基因预测,构建lncRNA TUG1-microRNAs-mRNAs调控网络。并运用FunRich平台对预测的靶基因进行Gene Ontology(GO)分析和KEGG信号转导通路富集分析。结果 TUG1在HCC中表达明显增高,随着肿瘤分级增高TUG1的表达呈上升趋势。lncRNA TUG1低表达患者的总生存期较高表达患者明显延长。TUG1上存在hsa-mir-122-5p、hsa-mir-200a-3p、hsa-mir-34c-3p、hsa-mir-629-3p这4个与HCC相关microRNAs的可能结合位点,从而调节下游245个靶基因,形成了lncRNA TUG1-microRNAs-mRNAs调控网络。在生物学过程中,microRNAs靶基因高度富集到碱基、核苷、核苷酸和核酸代谢调节等过程。KEGG pathway分析中,microRNAs靶基因高度富集到Syndecan、TRAIL等介导的信号通路。结论TUG1在HCC中表达水平增高,并与不良预后有关。利用生物信息学方法,可以从分子水平探究肿瘤发生机制,可为后续实验及临床诊疗提供有价值的信息。Objective To explore the significance of long non-coding RNA（lncRNA）taurine up-regulated gene 1（TUG1）in hepatocellular carcinoma（HCC）,to predict the target gene of TUG1,and to provide a reference for further study of TUG1 in HCC.Methods The differential expression of TUG1 in HCC was analyzed by using the UALCAN database and the survival analysis of TUG1 was performed.The target gene of TUG1 was predicted by RegRNA 2.0 biology software,HMDD,targetscan and microT-CDS,and the regulatory network of lncRNA TUG1-microRNAs-mRNAs was constructed.The predicted target gene was analyzed by Gene Ontology（GO）and KEGG signal transduction pathway enrichment by using FunRich platform.Results TUG1 expression in HCC was significantly increased,and the expression level of TUG1 increased generally with the increase of tumor grade.The overall survival of patients with low expression of lncRNA TUG1 was significantly longer than that of lncRNA TUG1 high expression patients.There were four possible binding sites of HCC related microRNAs（hsa-mir-122-5 p,hsa-mir-200 a-3 p,hsa-mir-34 c-3 p,hsa-mir-629-3 p）on TUG1,which regulated 245 downstream target genes and formed the regulatory network of lncRNA TUG1-microRNAs-mRNAs.In the biological process,microRNA target genes were highly enriched in the processes such as the regulation of nucleobase,nucleoside,nucleotide and nucleic acid metabolism.In KEGG pathway analysis,microRNA target genes were highly enriched to the signal pathways mediated by Syndecan and TRAIL.Conclusion TUG1 expression level in HCC increased.Increased expression of TUG1 is associated with poor prognosis in HCC.Bioinformatics methods can be used to explore the mechanism of tumorigenesis from the molecular level,which can provide valuable information for subsequent experiments and clinical diagnosis and treatment.

关 键 词：肝细胞癌 牛磺酸上调基因1 靶基因 生物信息学 

分 类 号：R735.7[医药卫生—肿瘤]