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Authors Fan Q, Liu B
Received 28 November 2017
Accepted for publication 3 March 2018
Published 1 May 2018 Volume 2018:11 Pages 2453—2466
DOI https://doi.org/10.2147/OTT.S158309
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Cristina Weinberg
Peer reviewer comments 4
Editor who approved publication: Dr Samir Farghaly
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