李璟波,周少华,夏晖,李少军,刘阳.hsa-miR-221调控非小细胞肺癌分子网络的生物信息学分析[J].转化医学杂志,2020,9(6):356-359
hsa-miR-221调控非小细胞肺癌分子网络的生物信息学分析
Bioinformatics analysis of hsa-miR-221 regulatory network in non-small-cell lung carcinoma
  
DOI:
中文关键词:  生物信息学  人miR-221  非小细胞肺癌  分子调控网络
英文关键词:Bioinformatics  Hsa-miR-221  Non-small-cell lung carcinoma (NCSLC)  Regulatory network
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作者单位
李璟波 解放军总医院第四医学中心胸外科
解放军总医院第一医学中心胸外科 
周少华 解放军总医院第六医学中心胸外科 
夏晖 解放军总医院第四医学中心胸外科 
李少军 解放军总医院第四医学中心胸外科 
刘阳 解放军总医院第一医学中心胸外科 
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中文摘要:
      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。
英文摘要:
      ObjectiveTo predict the regulatory network of hsa-miR-221 in non-small-cell lung carcinoma (NCSLC) using bioinformatics methods. MethodsThe 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. ResultsThe 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. ConclusionThe 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.
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