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Colorectal cancer (CRC) is one of the leading causes of cancer-associated death globally. Long non-coding RNAs (lncRNAs) have been identified as micro RNA (miRNA) sponges in a competing endogenous RNA (ceRNA) network and are involved in the regulation of mRNA expression. This study aims to construct a lncRNA-associated ceRNA network and investigate the prognostic biomarkers in CRC. A total of 38 differentially expressed (DE) lncRNAs, 23 DEmiRNAs and 27 DEmRNAs were identified by analysing the expression profiles of CRC obtained from The Cancer Genome Atlas (TCGA). These RNAs were chosen to develop a ceRNA regulatory network of CRC, which comprised 125 edges. Survival analysis showed that four lncRNAs, six miRNAs and five mRNAs were significantly associated with overall survival. A potential regulatory axis of ADAMTS9-AS2/miR-32/PHLPP2 was identified from the network. Experimental validation was performed using clinical samples by quantitative real-time PCR (qRT-PCR), which showed that expression of the genes in the axis was associated with clinicopathological features and the correlation among them perfectly conformed to the 'ceRNA theory'. Overexpression of ADAMTS9-AS2 in colon cancer cell lines significantly inhibited the miR-32 expression and promoted PHLPP2 expression, while ADAMTS9-AS2 knockdown had the opposite effects. The constructed novel ceRNA network may provide a comprehensive understanding of the mechanisms of CRC carcinogenesis. The ADAMTS9-AS2/miR-32/PHLPP2 regulatory axis may serve as a potential therapeutic target for CRC.
Pubmed ID: 31144439
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View all literature mentionsCollection of genome databases for vertebrates and other eukaryotic species with DNA and protein sequence search capabilities. Used to automatically annotate genome, integrate this annotation with other available biological data and make data publicly available via web. Ensembl tools include BLAST, BLAT, BioMart and the Variant Effect Predictor (VEP) for all supported species.
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View all literature mentionsIntegrated database resource consisting of 16 main databases, broadly categorized into systems information, genomic information, and chemical information. In particular, gene catalogs in completely sequenced genomes are linked to higher-level systemic functions of cell, organism, and ecosystem. Analysis tools are also available. KEGG may be used as reference knowledge base for biological interpretation of large-scale datasets generated by sequencing and other high-throughput experimental technologies.
View all literature mentionsBioconductor software package for Empirical analysis of Digital Gene Expression data in R. Used for differential expression analysis of RNA-seq and digital gene expression data with biological replication.
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View all literature mentionsCell line HT-29 is a Cancer cell line with a species of origin Homo sapiens (Human)
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