食管鳞癌中miRNA-mRNA调控网络的构建和信号通路分析

Construction of miRNA-mRNA regulatory network and signal pathway analysis in esophageal squamous cell carcinoma

摘要:

目的：构建食管鳞状细胞癌（esophageal squamous cell carcinoma，ESCC）中miRNA-mRNA的调控网络，对候选基因进行基因本体（gene ontology，GO）功能注释和京都基因与基因组百科全书（Kyoto encyclopedia of genes and genomes，KEGG）通路富集分析，为ESCC发生发展的分子机制研究提供一定的理论指导。方法：从GEO数据库中筛选ESCC组织中的差异表达miRNA（differentially expressed miRNA，DE miRNA）和差异表达基因（differentially expressed genes，DEGs），并用在线数据库预测调控DE miRNA的靶基因。对DE miRNA的靶基因及DEGs取交集得到候选基因，使用DAVID在线数据库对其进行GO富集分析和KEGG分析，并运用GEPIA网站进行生存分析。结果：筛选出4个DE miRNA（miR-34c-5p、miR-944、miR-133b、miR-139-5p），分析DE miRNA在ESCC组织和正常食管组织中的表达情况。候选基因GO富集分析表明其主要参与细胞增殖、凋亡、迁移等过程，KEGG分析表明其主要富集在PI3K/AKT、Rap1、P53信号通路，生存分析发现候选基因中的COL1A1、SOX4与食管癌较差的无病生存期（disease-free survival，DFS）有关。结论：miR-34c-5p、miR-944、miR-133b和miR-139-5p在ESCC中存在差异表达，可能在食管鳞癌的发生发展中发挥作用，且候选基因COL1A1、SOX4与食管癌较差的无病生存期相关。

Abstract:

Objective：We using bioinformatics methods to screen differentially expressed miRNA（DE miRNA） and its target genes and esophageal squamous cell carcinoma（ESCC） differentially expressed genes（DEGs） in ESCC，we perform GO and KEGG enrichment. Then，we screen for genes associated with the of esophageal squamous cell carcinoma. Methods：Gene expression profile datasets and microRNA（miRNA） expression profile datasets were downloaded from the NCBI gene expression omnibus（GEO） database，DE miRNA and DEGs in ESCC tissues were screened using GEO2R tool. The target genes of DE miRNAs were predicted by using the online databases TargetScan，StarBase，miRWalk and miRDB. The target genes of DE miRNA and DEGs were taken together，GO and KEGG enrichment analysis was performed using DAVID online database，the survival analysis was performed using GEPIA website. Results：Four DE miRNAs were screened from the GEO database（miR-34c-5p，miR-944，miR-133b and miR-139-5p expression） and the expression of DE miRNA in ESCC tissues and normal esophageal tissues were analyzed. GO enrichment analysis of can－didate genes indicated that it was mainly involved in cell proliferation，apoptosis，migration et al. KEGG enrichment analysis indicated that it was mainly enriched in PI3K/AKT、Rap1、P53 signaling pathway，survival analysis found COL1A1，SOX4 is associated with poor disease-free survival（DFS）. Conclusion：MiR-34c-5p，miR-944，miR-133b and miR-139-5p may play a role in the develop－ment of esophageal squamous cell carcinoma. Through the pre－dictive analysis of target genes of four DE miRNAs，it provides a theoretical basis for further research on the pathogenesis of esophageal squamous cell carcinoma.