肝癌相关hsa-miR-483-5p的靶基因预测及生物信息学分析

Target gene prediction and bioinformatics analysis of hepatocellular carcinoma related hsa-miR-483-5p

目的通过生物信息学分析方法预测miR-483-5p的靶基因和信号通路,为进一步分析其在肝癌发生、发展中的调控机制提供理论依据。方法利用starBase靶基因数据库预测hsa-miR-483-5p靶基因集,利用STRING数据库和Cytoscape软件构建miRNA潜在靶点蛋白质相互作用(PPI)网络图,再将预测的靶基因利用软件R 3.6.3进行基因本体(GO)功能富集分析及京都基因与基因组百科全书(KEGG)信号通路富集分析。结果hsa-miR-483-5p预测的靶基因一共278个。GO功能富集分析结果显示,hsa-miR-483-5p的靶基因主要富集在细胞的焦点粘连、细胞基质黏着小带、细胞-基质结等细胞组分;参与蛋白丝氨酸/苏氨酸激酶活性等分子功能(P值均<0.05)。KEGG信号通路富集分析表明,hsa-miR-483-5p的靶基因信号通路显著富集在焦点粘连通路和胰岛素信号通路(P值均<0.05)。其中,MAPK1和MAPK3同时出现在所有的细胞组分、分子功能和信号通路中,处于信号转导网络的核心位置。结论hsa-miR-483-5p可能通过靶基因参与多种生物学过程,推测其在肝癌中的作用可能与MAPK1和MAPK3的调控密切相关。

Objective The target genes and signaling pathways of miR-483-5p were predicted by bioinformatics analysis methods,providing a theoretical basis for further analysis of its regulatory mechanism in the occurrence and development of hepatocellular carcinoma(HCC).Methods StarBase database was used to predict hsa-miR-483-5p target gene set. STRING database and Cytoscape were used to build the miRNA potential target Protein-Protein Interaction(PPI) network, and the predicted target genes were analyzed by Gene Ontology(GO) function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) signal pathway enrichment analysis with R(3.6.3 version). Results A total of 278predicted genes were targeted by hsa-miR-483-5p. The GO enrichment analysis showed that the target genes of hsa-miR-483-5p were mainly enriched in cellular components such as focal adhesion, cell-matrix adhesion belt, cell-matrix junction, and they were involved in protein serine/threonine kinases(all P<0.05). KEGG signaling pathway analysis showed that the target genes of hsa-miR-483-5p were significantly enriched in focal adhesion pathway and insulin signaling pathway(P<0.05). MAPK1 and MAPK3 appeared simultaneously in all cell components, molecular functions, and signaling pathways, which located at the core of signal transduction network.Conclusion hsa-miR-483-5p may participate in a variety of biological processes through target genes, and its role in HCC may be closely related to the regulation of MAPK1 and MAPK3.