Yang Yuemei, Jia Binghan, Zhao Xiaoling, Wang Yao, Ye Weiliang
Department of R&D Technology Center, Beijing Zhicheng Biomedical Technology Co, Ltd, Beijing, China.
J Cell Biochem. 2019 Jun;120(6):10463-10483. doi: 10.1002/jcb.28332. Epub 2018 Dec 23.
Prostate adenocarcinoma is one of the most prevalent causes of cancer-related deaths in males worldwide. However, the underlying mechanisms remain poorly understood. Hence, it is important to identify specific and effective therapeutic targets, to be able to determine appropriate therapy and management. So, this study aimed to predict that miR-93-5p is an important oncogene in prostate cancer by bioinformatics analysis.
In this study, initially we identified differentially expressed genes (DEGs) and differently expressed miRNAs (DEMs) in the The Cancer Genome Atlas (TCGA) database, performed Gene Ontology (GO) and pathway enrichment analysis, then investigated the relationship between DEGs and DEMs, and finally through consulting the literature and retrieving the database, we found that miR-93-5p may play a major role in prostate cancer, so we predicted the expression and survival of miR-93-5p and its isomers by bioinformatics analysis, meanwhile, evaluated the function of miR-93-5p in vitro.
In total, 104 DEMs were differently expressed between prostate cancer and normal samples, including 56 downregulated ones and 48 upregulated ones; miR-93-5p (upregulated) was identified as a good biomarker. And 1904 DEGs were retrieved, including 794 downregulated ones and 1110 upregulated ones. We also obtained 1254 DEGs of the DEMs. In GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, the significantly enriched pathways involved pathway in focal adhesion, vascular smooth muscle contraction, and regulation of actin cytoskeleton. By the KEGG pathway, we got 16 target genes and 92 pathways of the miR-93-5p in prostate cancer. We also found that the miR-93-5p and its isomers can express in prostate cancer, and which with a high expression had a poor overall survival and a significant difference recurrence rate within 5 years. Further in vitro verification results demonstrated that the low expression of miR-93-5p can inhibit cell proliferation, migration, invasion, change cell cycle, and promote early apoptosis of PC-3 cells.
The miR-93-5p and its target genes were used to define important molecular targets that could serve as a prognostic and predictive marker in the treatment of prostate cancer. Further research on the function of the miR-93-5p and its target genes in the KEGG pathway could provide references for the treatment of prostate cancer.
前列腺腺癌是全球男性癌症相关死亡的最常见原因之一。然而,其潜在机制仍知之甚少。因此,识别特定且有效的治疗靶点,以便能够确定合适的治疗方法和管理措施非常重要。所以,本研究旨在通过生物信息学分析预测miR-93-5p是前列腺癌中的一个重要癌基因。
在本研究中,我们首先在癌症基因组图谱(TCGA)数据库中鉴定了差异表达基因(DEG)和差异表达miRNA(DEM),进行了基因本体论(GO)和通路富集分析,然后研究了DEG和DEM之间的关系,最后通过查阅文献和检索数据库,我们发现miR-93-5p可能在前列腺癌中起主要作用,因此我们通过生物信息学分析预测了miR-93-5p及其异构体的表达和生存情况,同时在体外评估了miR-93-5p的功能。
总共,前列腺癌和正常样本之间有104个DEM表达不同,包括56个下调的和48个上调的;miR-93-5p(上调)被鉴定为一个良好的生物标志物。并且检索到1904个DEG,包括794个下调的和1110个上调 的。我们还获得了DEM的1254个DEG。在GO和京都基因与基因组百科全书(KEGG)分析中,显著富集的通路涉及粘着斑、血管平滑肌收缩和肌动蛋白细胞骨架调节通路。通过KEGG通路,我们获得了前列腺癌中miR-93-5p的16个靶基因和92条通路。我们还发现miR-93-5p及其异构体可以在前列腺癌中表达,并且高表达者总生存期较差,5年内复发率有显著差异。进一步的体外验证结果表明,miR-93-5p的低表达可以抑制PC-3细胞的增殖、迁移、侵袭,改变细胞周期,并促进其早期凋亡。
miR-93-5p及其靶基因被用于定义重要的分子靶点,这些靶点可作为前列腺癌治疗中的预后和预测标志物。对miR-93-5p及其靶基因在KEGG通路中的功能进行进一步研究可为前列腺癌的治疗提供参考。