Department of Urology, The Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, China (mainland).
Department of Urology, People' Hospital of Guilin, Guilin, Guangxi, China (mainland).
Med Sci Monit. 2019 Apr 25;25:3041-3060. doi: 10.12659/MSM.915487.
BACKGROUND Bladder cancer is a multifactorial disease with increasing incidence and mortality. Genetic alterations and altered expressions of mRNAs, long non-coding RNAs (lncRNAs), and miRNAs have been shown to play important roles in the tumorigenesis of bladder cancer. However, the functions of key RNAs and their regulatory network in bladder cancer are still to be elucidated. MATERIAL AND METHODS RNA profiles were downloaded from The Cancer Genome Atlas (TCGA) database. The differentially expressed mRNAs, lncRNAs, and miRNAs in bladder cancer were acquired through analyses of data from 414 bladder cancer tissues and 19 normal bladder tissues. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis was performed by using "DAVID6.8" and the R package "ClusterProfile". Protein-protein interaction and competing endogenous RNA (ceRNA) networks were constructed by using "STRING" database and Cytoscape 3.6.2. Based on the clinical data and Cox regression, a prognosis model was established, and survival analysis was performed. RESULTS A total of 1819 mRNAs, 659 lncRNAs, and 160 miRNAs were identified as significantly differentially expressed in bladder cancer of which 52 mRNAs, 58 lncRNAs, and 22 miRNAs were incorporated in the ceRNA network. CFL2 and TPM2 were found to be downregulated and showed significant correlation to each other in bladder cancer. HOXB5 and 6 lncRNAs (ADAMTS9-AS1, AC112721.1, LINC00460, AC110491.1, LINC00163, and HCG22) were strongly associated with high-grade, disease stages, and overall survival. CONCLUSIONS In this study, we have identified differentially expressed mRNAs, lncRNAs, and miRNAs in bladder cancer which were strongly associated with oncogenesis and prognosis. Further experimental studies are necessary to validate these results.
膀胱癌是一种具有发病率和死亡率不断增加的多因素疾病。已表明遗传改变和 mRNA、长非编码 RNA（lncRNA）和 microRNA 的表达改变在膀胱癌的肿瘤发生中发挥重要作用。然而，关键 RNA 的功能及其在膀胱癌中的调控网络仍有待阐明。
从癌症基因组图谱（TCGA）数据库下载 RNA 图谱。通过分析 414 例膀胱癌组织和 19 例正常膀胱组织的数据，获得膀胱癌中差异表达的 mRNA、lncRNA 和 miRNA。使用“DAVID6.8”和 R 包“ClusterProfile”进行基因本体论和京都基因与基因组百科全书分析。通过“STRING”数据库和 Cytoscape 3.6.2 构建蛋白质-蛋白质相互作用和竞争内源性 RNA（ceRNA）网络。基于临床数据和 Cox 回归建立预后模型并进行生存分析。
共鉴定出 1819 个 mRNA、659 个 lncRNA 和 160 个 miRNA 在膀胱癌中显著差异表达，其中 52 个 mRNA、58 个 lncRNA 和 22 个 miRNA 包含在 ceRNA 网络中。在膀胱癌中发现 CFL2 和 TPM2 下调且相互之间呈显著相关性。HOXB5 和 6 个 lncRNA（ADAMTS9-AS1、AC112721.1、LINC00460、AC110491.1、LINC00163 和 HCG22）与高级别、疾病分期和总生存期密切相关。
在这项研究中，我们鉴定出膀胱癌中差异表达的 mRNAs、lncRNA 和 miRNA，它们与肿瘤发生和预后密切相关。需要进一步的实验研究来验证这些结果。
