Cao Dan, Wang Ying, Li Dajiang, Wang Lichun
Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, P.R. China.
Crit Rev Eukaryot Gene Expr. 2019;29(6):539-549. doi: 10.1615/CritRevEukaryotGeneExpr.2019028740.
Hepatocellular carcinoma (HCC) is a common and aggressive malignant neoplasm with an increasing incidence rate among cancers worldwide. This study aimed to establish a competing-endogenous RNA (ceRNA) network to further understand the ceRNA regulatory mechanism and pathogenesis in HCC. mRNA and miRNA expression data and corresponding clinical characteristics of HCC patients were downloaded from The Cancer Genome Atlas Data Portal. The different expression profiles of mRNA, lncRNA, and miRNA (referred to as DEmRNAs, DElncRNAs, and DEmiR-NAs, respectively) screened 374 HCC tumor tissues and 50 adjacent nontumor control tissues. The miRcode database was used to predict interactions between DElncRNAs and DEmiRNAs. The miRTarBase, miRDB, and TargetScan databases were used to retrieve miRNA-targeted mRNAs. The lncRNA-miRNA-mRNA ceRNA network was constructed based on matched DElncRNA-DEmiRNA and DEmiRNA-DEmRNA pairs. Functional enrichment analysis revealed the biological processes and pathways of DEmRNAs involved in the development of HCC. Key differentially expressed RNAs in the ceRNA network were further analyzed for their relationships with overall survival in HCC patients. A total of 1,982 mRNAs, 1,081 lncRNAs, and 126 miRNAs were identified as differentially expressed. The ceRNA network was constructed including 74 DElncRNAs, 35 DEmRNAs, and 16 DEmiRNAs. 13 DElncRNAs and 19 DEmRNAs were identified as prognosis-related biomarkers. Twenty-five Gene Ontology terms and 8 Kyoto Encyclopedia of Genes and Genomes pathways were found to be significantly enriched by DEmRNAs in the ceRNA network. Our results demonstrated tumor-specific mRNA, lncRNA, and miRNA expression patterns and enabled us to construct a ceRNA network that provided new insights into the molecular mechanisms of HCC. Key differentially expressed RNAs associated with total survival were also identified as promising biomarkers for survival prediction.
肝细胞癌（HCC）是一种常见且侵袭性强的恶性肿瘤，在全球癌症中的发病率呈上升趋势。本研究旨在建立一个竞争性内源性RNA（ceRNA）网络，以进一步了解HCC中的ceRNA调控机制和发病机制。从癌症基因组图谱数据门户下载了HCC患者的mRNA和miRNA表达数据以及相应的临床特征。通过筛选374个HCC肿瘤组织和50个相邻的非肿瘤对照组织，获得了mRNA、lncRNA和miRNA的差异表达谱（分别称为DEmRNAs、DElncRNAs和DEmiRNAs）。利用miRcode数据库预测DElncRNAs和DEmiRNAs之间的相互作用。使用miRTarBase、miRDB和TargetScan数据库检索miRNA靶向的mRNA。基于匹配的DElncRNA-DEmiRNA和DEmiRNA-DEmRNA对构建lncRNA-miRNA-mRNA ceRNA网络。功能富集分析揭示了参与HCC发生发展的DEmRNAs的生物学过程和通路。进一步分析ceRNA网络中关键的差异表达RNA与HCC患者总生存的关系。共鉴定出1982个差异表达的mRNA、1081个lncRNA和126个miRNA。构建的ceRNA网络包含74个DElncRNAs、35个DEmRNAs和16个DEmiRNAs。鉴定出13个DElncRNAs和19个DEmRNAs为预后相关生物标志物。发现ceRNA网络中的DEmRNAs显著富集了25个基因本体学术语和8条京都基因与基因组百科全书通路。我们的结果展示了肿瘤特异性的mRNA、lncRNA和miRNA表达模式，并使我们能够构建一个ceRNA网络，为HCC的分子机制提供了新的见解。与总生存相关的关键差异表达RNA也被鉴定为有前景的生存预测生物标志物。
