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基于一组特征性 microRNAs 对前列腺癌进行靶向的关键基因和信号通路的计算机识别。

In silico identification of key genes and signaling pathways targeted by a panel of signature microRNAs in prostate cancer.

机构信息

Symbiosis School of Biological Sciences, Symbiosis International (Deemed University), Lavale, Mulshi, Pune, 412115, India.

出版信息

Med Oncol. 2019 Apr 1;36(5):43. doi: 10.1007/s12032-019-1268-y.

Abstract

Accumulating evidence have suggested that some microRNAs are aberrantly expressed in prostate cancer. In our previous work, we had identified a panel of four differentially expressed microRNAs in prostate cancer. In the present study, we have investigated common molecular targets of this panel of miRNAs (DEMs) and key hub genes that can serve as potential candidate biomarkers in the pathogenesis and progression of prostate cancer. A joint bioinformatics approach was employed to identify differentially expressed genes (DEGs) in prostate cancer. Gene enrichment analysis followed by the protein-protein interaction (PPI) network construction and selection of hub genes was further performed using String and Cytoscape, respectively. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the identified hub genes was conducted using the Database for Annotation, Visualization and Integrated Discovery (DAVID) tool. In total, 496 genes were identified to be common targets of DEMs in prostate cancer and 13 key hub genes were identified from three modules of the PPI network of the DEGs. Further top five genes viz Rhoa, PI3KCA, CDC42, MAPK3, TP53 were used for Enrichment analysis which revealed their association with vital cellular and functional pathways in prostate cancer indicating their potential as candidate biomarkers in prostate cancer.

摘要

越来越多的证据表明,一些 microRNAs 在前列腺癌中表达异常。在我们之前的工作中,已经鉴定出一组在前列腺癌中差异表达的 microRNAs。在本研究中,我们研究了这组 microRNAs(差异表达 microRNAs)的常见分子靶标和关键枢纽基因,它们可以作为前列腺癌发病机制和进展的潜在候选生物标志物。采用联合生物信息学方法鉴定前列腺癌中的差异表达基因。使用 String 和 Cytoscape 分别进行基因富集分析,然后构建和选择蛋白质-蛋白质相互作用(PPI)网络的枢纽基因。使用数据库 for Annotation、Visualization and Integrated Discovery(DAVID)工具对鉴定出的枢纽基因进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)通路富集分析。总共鉴定出 496 个基因是前列腺癌中差异表达 microRNAs 的共同靶标,从 DEGs 的 PPI 网络的三个模块中鉴定出 13 个关键枢纽基因。进一步对前五个基因 viz Rhoa、PI3KCA、CDC42、MAPK3、TP53 进行富集分析,揭示了它们与前列腺癌中重要的细胞和功能途径的关联,表明它们作为前列腺癌候选生物标志物的潜力。

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