基于生物信息学的hsa-miR-32靶基因预测与功能分析

Bioinformatics analysis and prediction of hsa-miR-32 target genes

目的利用生物信息学方法,预测hsa-miR-32的靶基因并分析其功能,为深入研究其生物学功能提供指导和思路。方法利用miRBase数据库获取并分析不同物种的miR-32序列特征;从公共GEO(gene expression omnibus,GEO)数据库中下载不同疾病相关的microRNA表达谱芯片数据,通过miRGator v3.0在线工具和Qlucore Omics Explorer 3.0软件分析hsa-miR-32在不同疾病组织中表达情况;并用Pic Tar、DIANA-micro T-CDS 7.0、PITA及miRanda等方法预测hsa-miR-32靶基因,对获得的靶基因集合分别进行功能富集分析(gene ontology analysis)和生物通路富集分析(pathway enrichment analysis)。结果 miR-32在不同物种间高度保守。与癌旁正常组织相比,hsamiR-32在子宫癌、结直肠癌、胰腺癌、前列腺癌、乳腺癌等多种癌组织中表达异常(均有P<0.05)。包括已被证实的靶基因,共得到168个候选基因,这些靶基因主要参与调控基因表达、细胞增殖、信号转导、细胞死亡等生物学过程(均有P<0.05),涉及小细胞肺癌、前列腺癌、胶质瘤、黑素瘤等疾病相关通路,以及p53等肿瘤相关信号通路和细胞周期等信号转导通路(均有P<0.05)。结论 hsa-miR-32功能广泛,与癌症的发生、发展密切相关。

Objective Bioinformatics software and database were applied to predict and analyze target genes and functions of hsa-miR-32, in order to provide a basis for the study of the mechanism of hsa-miR-32 and its target genes in cancer. Methods The sequence of miR-32 was got from miRBase database. The microarray data of disease were down- loaded from the Gene Expression Omnibus（GEO） and the expression level of hsa-miR-32 in disease was analysed by miR- Gator and Qlucore Omics Explorer. PicTar, DIANA-microT-CDS, PITA and miRanda algorithm were used to predict target genes of hsa-miR-32. Combined with validated target genes, the gene set was analyzed by gene ontology（GO） and pathway enrichment. Results miR-32 was highly conserved among different species. Different expression levels of hsa-miR-32 were observed in different cancer tissues compared with adjacent normal tissues（ all P 〈0. 05）. Gene ontology analysis in- dicated that 168 target genes were mainly enriched in positive regulation of gene expression, negative regulation of cell pro- liferation, negative regulation of signal transduction, cell death and other biology processes（ all P 〈 0. 05 ）. KEGG pathway analysis showed that these genes were mostly involved in small cell lung cancer, prostate cancer, glioma, melanoma, path- ways in cancer, p53 signaling pathway and cell cycle（ all P 〈 0. 05 ）. Conclusions The target genes of hsa-miR-32 may have extensive functions and be closely related with cancer.