OncoTargets and Therapy (May 2018)
Comprehensive analysis of a long noncoding RNA-associated competing endogenous RNA network in colorectal cancer
Abstract
Qiaowei Fan,1,2 Bingrong Liu1 1Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China; 2Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, Heilongjiang, People’s Republic of China Purpose: This study was aimed to develop a lncRNA-associated competing endogenous RNA (ceRNA) network to provide further understanding of the ceRNA regulatory mechanism and pathogenesis in colorectal cancer (CRC).Patients and methods: Expression profiles of mRNAs, lncRNAs, and miRNAs, and clinical information for CRC patients were obtained from The Cancer Genome Atlas. The differentially expressed mRNAs, lncRNAs, and miRNAs (referred to as “DEmRNAs”, “DElncRNAs”, and “DEmiRNAs”, respectively) were screened out between 539 CRC samples and 11 normal samples. The interactions between DElncRNAs and DEmiRNAs were predicted by miRcode. The DEmRNAs targeted by the DEmiRNAs were retrieved according to TargetScan, miRTarBase, and miRDB. The lncRNA–miRNA–mRNA ceRNA network was constructed based on the DEmiRNA–DElncRNA and DEmiRNA–DEmRNA interactions. Functional enrichment analysis revealed the biological processes and pathways of DEmRNAs involved in the development of CRC. Key lncRNAs were further analyzed for their associations with overall survival and clinical features of CRC patients.Results: A total of 1,767 DEmRNAs, 608 DElncRNAs, and 283 DEmiRNAs were identified as CRC-specific RNAs. Three hundred eighty-two DEmiRNA–DElncRNA interactions and 68 DEmiRNA–DEmRNA interactions were recognized according to the relevant databases. The lncRNA–miRNA–mRNA ceRNA network was constructed using 25 DEmiRNAs, 52 DEmRNAs, and 64 DElncRNAs. Two DElncRNAs, five DEmiRNAs, and six DEmRNAs were demonstrated to be related to the prognosis of CRC patients. Four DElncRNAs were found to be associated with clinical features. Twenty-eight Gene Ontology terms and 10 Kyoto Encyclopedia of Genes and Genomes pathways were found to be significantly enriched by the DEmRNAs in the ceRNA network.Conclusion: Our results showed cancer-specific mRNA, lncRNA, and miRNA expression patterns and enabled us to construct an lncRNA-associated ceRNA network that provided new insights into the molecular mechanisms of CRC. Key RNA transcripts related to the overall survival and clinical features were also found with promising potential as biomarkers for diagnosis, survival prediction, and classification of CRC. Keywords: colorectal cancer, competing endogenous RNA network, long noncoding RNA, survival analysis
