EGFR突变相关miR-335靶基因预测及其功能的生物信息学分析

Bioinformatics analysis of target gene prediction and functions of miR-335 related to EGFR mutation

目的:通过筛选肺癌组织中表皮生长因子受体(epidermal growth factor receptor,EGFR)突变差异表达的microRNAs(miRs),并对其进行靶基因预测及功能的生物信息学分析,以期为miR与EGFR在肺癌中潜在的相互作用机制研究奠定基础。方法:利用TaqMan低密度芯片(TaqMan Low Density Array,TLDA)在4对肺癌组织中筛选EGRF突变差异表达的miRs。应用miRanda、PicTar和TargetScan数据库进行靶基因预测,并通过DAVID数据库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:miR-335在配对肺癌组织样本间差异表达值ΔΔC(tcycle threshold)的绝对值均>1,预测其有57个靶基因,功能主要集中于通道调节因子活性等8类分子(P<0.05)和RNA代谢调节等22类生物学过程(P<0.05)。分析结果未提示有显著富集的细胞组分和信号转导通路(P>0.05)。结论:本研究虽然未明确提示miR-335与EGFR具有直接作用,但是其参与的调控网络可能与EGFR具有密切联系。

Objective： This study measured the expression of microRNAs （miRs） between paired lung cancer tissues with and without epidermal growth factor receptor （EGFR） mutation and then bioinformatically predicted the target genes. The functions of miRs were analyzed to provide basis for the potential regulator mechanism between miR and EGFR in the future. Methods： The TaqMan low-density array was applied to identify the miRs differently expressed between 4 paired lung cancer tissues with and without EGFR mutation. The target genes of miR-335 were screened using miranda, PicTar, and TargetScan databases. Subsequent bioinformatics analysis of these target genes was performed by gene ontology （GO） and KEGG pathway analyses using the DAVID database. Results： The miR-335 expression between paired lung cancer tissues was different. A total of 57 predicted target genes of miR-335 were found. The gene set was mainly located in eight molecular functions （P〈0.05）, such as channel regulator activity, among others, and 22 biological processes （P〈0.05）, such as regulation of RNA metabolic process, among others. GO cellular component and KEGG pathway analyses found no significant result. Conclusion： Results showed that miR-335 had no direct effect on EGFR. However, the regulatory network involving miR-335 might be closely associated with EGFR.