摘要
目的应用生物信息学的方法研究hsa-miR-221在非小细胞肺癌(non-small cell lung carcinoma,NSCLC)中的分子调控网络。方法运用UCSC基因组浏览器、人类miRNA疾病数据库、TF-miRNA结合数据库、miRNA靶基因预测数据库、GeneCards数据库、肺癌相关因子整合数据库和转录因子结合谱数据库等,研究hsa-miR-221上游转录因子、下游靶基因及与其有相互作用的lncRNA的多个调控途径,绘制hsa-miR-221在NSCLC中分子调控网络。利用GEO数据库验证关键基因。结果UCSC数据库显示hsa-miR-221位于X染色体,在多个物种中保守。hsa-miR-221与多种癌症包括NSCLC相关。分析表明hsa-miR-221受6个与NSCLC相关的转录因子如MYC、MYCN等的调控,同时又调控下游基因PTEN、RB1和BCL2等26个基因。另外,lncRNA基因GAS5、HOTAIR和TUG1及其转录因子Snail、n-MYC、ARNT和SOX5等也可能参与调控hsa-miR-221,从而构成一个以hsa-miR-221为核心的调控网络,在NSCLC的发生和发展中起重要作用。通过对GEO数据库hsa-miR-221高表达NSCLC细胞系差异基因分析,最终验证了5个基因。结论用生物信息学的方法预测hsa-miR-221的分子调控网络,为阐明其调控NSCLC的发病机制提供指导。
Objective To predict the regulatory network of hsa-miR-221 in non-small-cell lung carcinoma(NCSLC)using bioinformatics methods.Methods The UCSC gene browser,HMDD,TransmiR,miRwalk,Genecards,IHLDB.rf and ConSite were employed in the present study.The upstream transcription factor,downstream target genes and the interactive lncRNA of hsa-miR-221 were studied by different online databases to determine the regulatory network of hsa-miR-221.Key genes were verified with GEO database.Results The UCSC gene browser showed that hsa-miR-221 was located in chromosome X and had high conservation in lots of organisms.The hsa-miR-221 was related with many carcinoma,including NSCLC.Combined all the results,it was postulated that hsa-miR-221 was regulated by transcription factors including MYC and MYCN,and at the same time it could regulate the target genes PTEN、RB1 and BCL2.lncRNA GAS5、HOTAIR、TUG1 and its transcription factors Snail、n-MYC、ARNT and SOX5 could also interact with hsa-miR-221.All the relative genes consisted of a regulatory network in the process of NSCLC.Through the analysis of differential genes of NSCLC cell lines with high expression of hsa-mir-221 in GEO database,five genes were finally verified.Conclusion The regulatory network of hsa-miR-221 in NSCLC is very complex.The results provides a good guideline for deeper insights into the pathogenesis of NSCLC and valuable guideline for the further research.
作者
李璟波
周少华
夏晖
李少军
刘阳
LI Jingbo;ZHOU Shaohua;XIA Hui;LI Shaojun;LIU Yang(Department of Chest Surgery,the Fourth Medical Center,Chinese PLA General Hospital,Beijing 100048,China;Department of Chest surgery,the First Medical Center,Chinese PLA General Hospital,Beijing 100853,China;Department of Chest Surgery,the Sixth Medical Center,Chinese PLA General Hospital,Beijing 100048,China)
出处
《转化医学杂志》
2020年第6期356-359,391,共5页
Translational Medicine Journal
