肺癌遗传易感差异表达miRNA的筛选及生物信息学分析

目的肺癌是目前我国死亡率最高的恶性肿瘤,发病率和病死率持续升高,且预后较差,患者的5年生存率小于15%,严重威胁人们的健康。筛选肺癌遗传易感差异表达的miRNA,分析差异表达的miRNA的靶基因功能,可为进一步研究miRNA在肺癌发生发展过程中的作用提供实验基础。方法采用高通量测序技术检测海南地区汉族肺癌患者和对照患者血清中差异表达的miRNA,通过生物信息学方法预测差异miRNAs的靶基因,并对靶基因进行GO功能富集分析、KEGG信号通路分析和蛋白相互作用分析。结果肺癌患者和对照患者共筛选出3个显著差异表达的miR-NA (P<0.05,|log2 (Fold Change)|≥1),且均呈下调状态。差异表达miRNAs所预测的靶基因显著参与癌症通路、轴突导向通路、代谢通路,NUFIP2、PLAGL2、IGF1R基因编码的蛋白在互作网络中具有重要作用。结论海南地区肺癌患者和对照患者间存在3个差异表达的miRNAs,这些miRNAs可能通过调控癌症、轴突导向、代谢等信号通路,调节下游靶蛋白参与肺癌的发生过程。

Screening and bioinformatics analysis of differentially expressed miRNAs contribute to lung cancer susceptibility

Objective Lung cancer has the highest mortality rate in the world. It's morbidity and mortality continue to rise with poor prognosis, the 5-year survival rate of lung cancer patients is less than 15%, which seriously threatens people's health. To screen out the differentially expressed miRNAs contribute to lung cancer susceptibility and analyze the function of the target genes, that can provide experimental basis for further study of the role of miRNA in the development and progression of lung cancer. Methods Next-generation sequencing was used to screen out differentially expressed miRNAs between lung cancer and control in Hainan Han population. Bioinformatics method was used to predict the target genes of differential miRNAs, and which were analyzed with GO enrichment analysis, KEGG pathway analysis, and protein interaction analysis. Results There were 3 differentially expressed miRNAs (P<0.05, |log2 (Fold Change)|≥1) between lung cancer and control, and all down regulated. The bioinformatics results showed that these target genes binding to miRNAs were enriched in cancer pathways, axon guidance and metabolic pathways. The main target genes of NUFIP2, PLAGL2 and IGF1R played an important role in the interaction network. Conclusions Three differentially expressed miRNAs were found between lung cancer and control, which may regulate the down-stream target proteins and thus be involved in the process of lung cancer via cancer pathways, axon guidance and metabolic pathways.