Shaji Sanu K, Sunilkumar Damu, Mahalakshmi N V, Kumar Geetha B, Nair Bipin G
School of Biotechnology, Amrita Vishwa Vidyapeetham, Kollam, Kerala 690525, India.
Oncol Lett. 2019 Aug;18(2):1938-1948. doi: 10.3892/ol.2019.10521. Epub 2019 Jun 24.
Glioblastoma multiforme (GBM) is one of the most malignant types of glioma known for its reduced survival rate and rapid relapse. Previous studies have shown that the expression patterns of different microRNAs (miRNA/miR) play a crucial role in the development and progression of GBM. In order to identify potential miRNA signatures of GBM for prognostic and therapeutic purposes, we downloaded and analyzed two expression data sets from Gene Expression Omnibus profiling miRNA patterns of GBM compared with normal brain tissues. Validated targets of the deregulated miRNAs were identified using MirTarBase, and were mapped to Search Tool for the Retrieval of Interacting Genes/Proteins, Database for Annotation, Visualization and Integrated Discovery and Kyoto Encyclopedia of Genes and Genomes databases in order to construct interaction networks and identify enriched pathways of target genes. A total of 6 miRNAs were found to be deregulated in both expression datasets studied. Pathway analysis demonstrated that most of the target genes were enriched in signaling cascades connected to cancer development, such as 'Pathways in cancer', 'Focal adhesion' and 'PI3K-Akt signaling pathway'. Of the five target genes that were enriched in the glioblastoma pathway, in the WikiPathway database, both HRas proto-oncogene, GTPase and MET proto-oncogene, receptor tyrosine kinase target genes of hsa-miR-139-5p, were found to be significantly associated with patient survival. The present study may thus form the basis for further exploration of hsa-miR-139-5p, not only as a therapeutic agent, but also as a diagnostic biomarker for GBM as well as a predictive marker for patient survival.
多形性胶质母细胞瘤(GBM)是最恶性的胶质瘤类型之一,以其低生存率和快速复发而闻名。先前的研究表明,不同微小RNA(miRNA/miR)的表达模式在GBM的发生和发展中起着关键作用。为了确定GBM潜在的miRNA特征用于预后和治疗,我们从基因表达综合数据库下载并分析了两个表达数据集,比较了GBM与正常脑组织的miRNA谱。使用MirTarBase鉴定失调miRNA的验证靶点,并将其映射到基因/蛋白质相互作用检索搜索工具、注释、可视化和综合发现数据库以及京都基因与基因组百科全书数据库,以构建相互作用网络并识别靶基因的富集途径。在所研究的两个表达数据集中共发现6种miRNA失调。通路分析表明,大多数靶基因富集于与癌症发展相关的信号级联反应,如“癌症通路”、“粘着斑”和“PI3K-Akt信号通路”。在胶质母细胞瘤通路中富集的五个靶基因中,在WikiPathway数据库中,hsa-miR-139-5p的HRas原癌基因、GTP酶和MET原癌基因、受体酪氨酸激酶靶基因均被发现与患者生存显著相关。因此,本研究可能为进一步探索hsa-miR-139-5p奠定基础,其不仅可作为一种治疗药物,还可作为GBM的诊断生物标志物以及患者生存的预测标志物。