生长激素腺瘤中差异表达的微小RNAs及其靶基因的相关生物信息学分析

Bioinformatics analysis of differentially expressed miRNAs and their target genes in growth hormone-secreting pituitary adenoma

目的探讨垂体生长激素(GH)细胞腺瘤中差异表达的微小RNAs(miRNAs)及其靶基因的生物学功能和两者的调控关系。方法利用miRDB、miRwalk、Targetscan7.2及starbase数据库对差异表达的miRNAs进行靶基因预测并对靶基因进行GO、KEGG和蛋白-蛋白相互作用网(PPI)分析,随后筛选出有意义的核心靶基因,取核心靶基因和数据库的mRNAs测序结果进行对比,构建可视化的miRNAs-靶基因调控关系网。结果以蛋白相互作用程度≥20为标准,本研究得到113个上调的miRNAs核心靶基因和128个下调的miRNAs核心靶基因,进一步取交集得到13个目的核心靶基因,这些基因主要涉及的通路为泛素介导蛋白水解通路,其相对应的调控miRNAs为miR-15b、miR-365、miR-32-3p、miR-486-5p。结论本研究应用生物信息学分析工具构建了与GH细胞腺瘤密切相关的miRNAs-核心靶基因相互调控网,发掘了一些可能与GH细胞腺瘤发病机制和病理过程有关的蛋白和通路。

Objective To explore the biological functions of differentially expressed miRNAs and their target genes,and their regulatory relations in growth hormone(GH)-secreting pituitary adenoma.Methods Four databases(miRDB,miRwalk,Targetscan7.2 and Starbase)were used to predict the target genes of differentially expressed miRNAs in GH-secreting pituitary adenoma,and GO,KEGG and protein-protein interaction network(PPI)analyses were performed on the target genes.Meaningful hub target genes were screened out and compared with mRNA sequencing results from the database;and then,a visual miRNA-target gene interaction network was constructed.Results Totally,113 up-regulated miRNAs target genes and 128 down-regulated miRNAs target genes were obtained with the protein interaction degree≥20.Further intersection was conducted to obtain 13 hub target genes;these genes were mainly involved in ubiquitin mediated proteolysis pathway.The regulatory miRNAs of the hub target genes were miR-15b,miR-365,miR-32-3p,and miR-486-5p.Conclusion A miRNAs-hub target gene mutual regulation network closely related to GH-secreting pituitary adenoma is constructed with bioinformatics analysis tools,and some potential proteins and pathways related to the pathogenesis and pathological process of GH-secreting pituitary adenoma are discovered.