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Construction of lncRNA-associated ceRNA networks to identify prognostic lncRNA biomarkers for glioblastoma.
Journal of Cellular Biochemistry ( IF 3.0 ) Pub Date : 2020-04-10 , DOI: 10.1002/jcb.29625
Zhendong Liu 1, 2 , Xiaoxiong Wang 1, 2 , Guang Yang 1, 2 , Chen Zhong 1, 2 , Ruotian Zhang 1, 2 , Junyi Ye 1, 2 , Yingqiang Zhong 1, 2 , Junlong Hu 1, 2 , Beylerli Ozal 1, 2, 3 , Shiguang Zhao 1, 2
Affiliation  

Long noncoding RNAs (lncRNAs) serve as competitive endogenous RNAs (ceRNAs) that play significant regulatory roles in the pathogenesis of tumors. However, the role of lncRNAs, especially the lncRNA-related ceRNA regulatory network, in glioblastoma (GBM) has not been fully elucidated. The goal of the current study was to construct lncRNA-microRNA-mRNA-related ceRNA networks for further investigation of their mechanism of action in GBM. We downloaded data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases and identified differential lncRNAs, microRNAs (miRNAs), and messenger RNAs (mRNAs) associated with GBM. A ceRNA network was constructed and analyzed to examine the relationship between lncRNAs and patients' overall survival. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGGs) were used to analyze the related mRNAs to indirectly explain the mechanism of action of lncRNAs. The potential effective drugs for the treatment of GBM were identified using the connectivity map (CMap). After integrated analysis, we obtained a total of 210 differentially expressed lncRNAs, 90 differentially expressed miRNAs, and 2508 differentially expressed mRNAs (DEmRNAs) from the TCGA and GEO databases. Using these differential genes, we constructed a lncRNA-associated ceRNA network. Six lncRNAs in the ceRNA network were associated with the overall survival of patients with GBM. Through KEGG analysis, it was found that the DEmRNAs involved in the network are related to cancer-associated pathways, for instance, mitogen-activated protein kinase and Ras signaling pathways. CMap analysis revealed four small-molecule compounds that could be used as drugs for the treatment of GBM. In this study, a multi-database joint analysis was used to construct a lncRNA-related ceRNA network to help identify the regulatory functions of lncRNAs in the pathogenesis of GBM.

中文翻译:

构建 lncRNA 相关的 ceRNA 网络以识别胶质母细胞瘤的预后 lncRNA 生物标志物。

长链非编码 RNA (lncRNA) 作为竞争性内源性 RNA (ceRNA),在肿瘤的发病机制中发挥重要的调控作用。然而,lncRNAs,尤其是lncRNA相关的ceRNA调控网络,在胶质母细胞瘤(GBM)中的作用尚未完全阐明。本研究的目标是构建 lncRNA-microRNA-mRNA 相关的 ceRNA 网络,以进一步研究它们在 GBM 中的作用机制。我们从癌症基因组图谱 (TCGA) 和基因表达综合 (GEO) 数据库下载数据,并确定了与 GBM 相关的差异 lncRNA、microRNA (miRNA) 和信使 RNA (mRNA)。构建并分析了 ceRNA 网络,以检查 lncRNA 与患者总生存率之间的关系。使用基因本体论(GO)和京都基因与基因组百科全书(KEGGs)分析相关mRNA,间接解释lncRNAs的作用机制。使用连接图 (CMap) 确定了治疗 GBM 的潜在有效药物。经过综合分析,我们从TCGA和GEO数据库中总共获得了210个差异表达的lncRNAs、90个差异表达的miRNAs和2508个差异表达的mRNAs(DEmRNAs)。利用这些差异基因,我们构建了一个 lncRNA 相关的 ceRNA 网络。ceRNA 网络中的 6 个 lncRNA 与 GBM 患者的总生存期相关。通过KEGG分析发现,参与网络的DEmRNAs与癌症相关通路有关,例如丝裂原活化蛋白激酶和Ras信号通路。CMap 分析揭示了四种可用作治疗 GBM 药物的小分子化合物。本研究采用多数据库联合分析构建lncRNA相关的ceRNA网络,以帮助识别lncRNA在GBM发病机制中的调控功能。
更新日期:2020-04-10
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