Wang Jiawu, Zhang Chengyao, Wu Yan, He Weiyang, Gou Xin
1Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Yuzhong District, Chongqing, China.
2Department of Head and Neck Cancer Center, Chongqing University Cancer Hospital & Chongqing Cancer Institute & Chongqing Cancer Hospital, Shapingba District, Chongqing, China.
Cancer Cell Int. 2019 Dec 3;19:327. doi: 10.1186/s12935-019-1052-2. eCollection 2019.
The aim of this study was to investigate the regulatory network of lncRNAs as competing endogenous RNAs (ceRNA) in bladder urothelial carcinoma (BUC) based on gene expression data derived from The Cancer Genome Atlas (TCGA).
RNA sequence profiles and clinical information from 414 BUC tissues and 19 non-tumor adjacent tissues were downloaded from TCGA. Differentially expressed RNAs derived from BUC and non-tumor adjacent samples were identified using the R package "edgeR". Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was performed using the "clusterProfiler" package. Gene ontology and protein-protein interaction (PPI) networks were analyzed for the differentially expressed mRNAs using the "STRING" database. The network for the dysregulated lncRNA associated ceRNAs was then constructed for BUC using miRcode, miRTarBase, miRDB, and TargetScan. Cox regression analysis was performed to identify independent prognostic RNAs associated with BUC overall survival (OS). Survival analysis for the independent prognostic RNAs within the ceRNA network was calculated using Kaplan-Meier curves.
Based on our analysis, a total of 666, 1819 and 157 differentially expressed lncRNAs, mRNAs and miRNAs were identified respectively. The ceRNA network was then constructed and contained 59 lncRNAs, 23 DEmiRNAs, and 52 DEmRNAs. In total, 5 lncRNAs (HCG22, ADAMTS9-AS1, ADAMTS9-AS2, AC078778.1, and AC112721.1), 2 miRNAs (hsa-mir-145 and hsa-mir-141) and 6 mRNAs (ZEB1, TMEM100, MAP1B, DUSP2, JUN, and AIFM3) were found to be related to OS. Two lncRNAs (ADAMTS9-AS1 and ADAMTS9-AS2) and 4 mRNA (DUSP2, JUN, MAP1B, and TMEM100) were validated using GEPIA. Thirty key hub genes were identified using the ranking method of degree. KEGG analysis demonstrated that the majority of the DEmRNAs were involved in pathways associated with cancer.
Our findings provide an understanding of the important role of lncRNA-related ceRNAs in BUC. Additional experimental and clinical validations are required to support our findings.
本研究旨在基于来自癌症基因组图谱（TCGA）的基因表达数据，研究长链非编码RNA（lncRNA）作为竞争性内源性RNA（ceRNA）在膀胱尿路上皮癌（BUC）中的调控网络。
从TCGA下载414例BUC组织和19例非肿瘤邻近组织的RNA序列图谱及临床信息。使用R包“edgeR”鉴定BUC和非肿瘤邻近样本中差异表达的RNA。使用“clusterProfiler”包进行京都基因与基因组百科全书（KEGG）通路分析。使用“STRING”数据库对差异表达的mRNA进行基因本体论和蛋白质-蛋白质相互作用（PPI）网络分析。然后使用miRcode、miRTarBase、miRDB和TargetScan构建BUC中失调的lncRNA相关ceRNA网络。进行Cox回归分析以鉴定与BUC总生存期（OS）相关的独立预后RNA。使用Kaplan-Meier曲线计算ceRNA网络中独立预后RNA的生存分析。
基于我们的分析，分别鉴定出666个、1819个和157个差异表达的lncRNA、mRNA和miRNA。然后构建了ceRNA网络，其中包含59个lncRNA、23个差异表达的miRNA（DEmiRNA）和52个差异表达的mRNA（DEmRNA）。总共发现5个lncRNA（HCG22、ADAMTS9-AS1、ADAMTS9-AS2、AC078778.1和AC112721.1）、2个miRNA（hsa-mir-145和hsa-mir-141）和6个mRNA（ZEB1、TMEM100、MAP1B、DUSP2、JUN和AIFM3）与OS相关。使用GEPIA验证了2个lncRNA（ADAMTS9-AS1和ADAMTS9-AS2）和4个mRNA（DUSP2、JUN、MAP1B和TMEM100）。使用度排名方法鉴定出30个关键枢纽基因。KEGG分析表明，大多数DEmRNA参与了与癌症相关的通路。
我们的研究结果有助于理解lncRNA相关ceRNA在BUC中的重要作用。需要进一步的实验和临床验证来支持我们的研究结果。
