食管鳞癌发生发展相关miRNA的筛选及其靶向mRNA生物学功能分析

Screening miRNAs related to development and progression of esophageal squamous cell carcinoma and biological functions of the targeted mRNAs

目的筛选食管鳞癌发生发展相关的miRNA及其靶向mRNA,并对靶向mRNA进行生物学功能分析。方法从GEO数据库下载两张食管鳞癌组织芯片(GSE75241、GSE114110),通过R语言limma函数包筛选两张芯片差异表达的mRNA和miRNA。利用FunRich3.1.3软件预测差异表达miRNA调控的靶基因,接着利用Cytoscapev3.1.1软件构建差异表达miRNA-mRNA调控网络图,并且筛选出节点度4~8的miRNA。最后利用DAVID在线工具对miRNA-mRNA调控网络中的mRNAs进行生物学功能与信号通路分析。结果与正常食管黏膜上皮组织相比,在食管鳞癌组织样品中筛选出114个差异表达miRNAs,其中42个表达下调、72个表达上调;另外筛选出224个差异表达mRNAs,124个表达上调、100个表达下调。miRNA-mRNA调控网络包括66个miRNA-mRNA关系对,其中具有较高节点度的miRNA为hsa-miR-92b-3p、hsa-miR-195-5p、hsa-miR-143-3p,mRNA为HAS2、ITGA6、COL1A1等。miRNA-mRNA调控网络中mRNAs主要富集在细胞外基质、成骨作用、维生素应答、血小板α颗粒等基因本体功能,参与ECM-受体相互作用、黏着斑、PI3K-Akt、TGF-β等多条通路。结论食管鳞癌发生发展相关miRNA有hsa-miR-195-5p、hsa-miR-143-3p、hsa-miR-31-5p、hsa-miR-127-3p,靶向mRNA主要有细胞外基质、成骨作用等生物学功能,参与的信号通路有ECM-受体相互作用、黏着斑、PI3K-Akt、TGF-β等通路。

Objective esophageal squamous cell carcinoma,and to analyze the biological functions of targeted mRNAs.Methods rays(GSE75241,GSE114110)were downloaded from the Gene Explanation Omnibus(GEO)database. The differentially expressed mRNAs and miRNAs of the two microarrays were screened by the Limma function package of R language. Funrich3. 1. 3 software was used to predict the target genes regulated by differentially expressed miRNAs. Then Cytoscapev3. 1. 1 software was used to construct the regulatory network map of differentially expressed miRNA-mRNA,and the genes with node degree of 4-8 were screened out. Finally,we used the DAVID online tool to analyze the biological functions and signal pathways of mRNAs in the miRNA-mRNA regulatory network.Results esophageal mucosal epithelia,114 differentially expressed miRNAs were screened out in the esophageal squamous cell carcinoma samples,of which 42 were down-regulated and 72 were up-regulated. In addition,224 differentially expressed mRNAs were screened out,of which 124 were up-regulated and 100 were down-regulated. The miRNA-mRNA regulatory network included 66 miRNA-mRNA relationship pairs,among which the gene miRNAs with high node degree were hsa-miR-92B-3p,hsa-miR-195-5p,hsa-miR-143-3p,etc;mRNAs were HAS2,ITGA6,COL1A1 and so on. These differentially expressed mRNAs were mainly enriched in GO terms such as extracellular matrix,osteogenesis,vitamin response,platelet α granules,etc. and participated multiple pathways such as ECM-receptor interaction,adhesion plaque,PI3K-Akt,TGF-β,etc.Conclusion cell carcinoma include hsa-miR-195-5p, hsa-miR-143-3p, hsa-miR-31-5p, hsa-miR-127-3p, and the target-ed mRNAs mainly have extracellular matrix,osteogenesis,and other biological functions,and the signal pathways includeECM-receptor interaction,focal adhesion,PI3K-Akt,TGF-β,and other pathways.