Construction and analysis of lncRNA-associated ceRNA network identified potential prognostic biomarker in gastric cancer.

ABSTRACT

BACKGROUND: Long non-coding RNAs (lncRNAs) are defined as non-coding RNA (ncRNA) with transcripts longer than 200 nucleotides with tissue specificity. Recently it has been found participate in cancer tumorigenesis and progression via transcriptional regulation, post-transcriptional regulation and epigenetic gene regulation. Competitive endogenous RNA (ceRNA) hypothesis assume that lncRNAs compete the target RNA by sponging the common miRNA response elements (MREs) to complete the post-transcriptional regulation. To explore the function and mechanisms of lncRNAs as ceRNAs in gastric cancer (GC), this study performed a genome-wide analysis. METHODS: The lncRNAs, mRNAs and microRNAs (miRNAs) profiles of 375 GC samples and 32 normal samples were obtained from The Cancer Genome Atlas (TCGA) Stomach Adenocarcinoma (STAD) datasets. The data was standardized with a cross match in the miRBase (a database at http//www.mirbase.org/), which made 365 samples as the analysis objects. We identify differentially expressed RNAs (DERNAs), including differentially expressed mRNAs (DEmRNAs), differentially expressed miRNAs (DEmiRNAs) and differentially expressed lncRNAs (DElncRNAs) by applying edge R package with thresholds of |log2FC| >2 and false discovery rate (FDR) <0.01. The potential RNAs for the gastric ceRNA network were screened out from the DERNAs based on "ceRNA hypothesis". The further construction of the network and analysis of its topological properties were performed by Cytoscape. Gene oncology (GO) function enrichment was analyzed by BINGO plugin of Cytoscape. Survival analysis was estimated according to Kaplan-Meier curve analysis. RESULTS: The constructed gastric ceRNA network involved 61 mRNAs, 44 lncRNAs and 22 miRNAs. Five lncRNAs out of the DElncRNAs, namely MIR100HG, MAGI2-AS3, AC080038.1, AC010478.1 and MEF2C-AS1, were found mostly involved in the network. The lncRNA AL139147 were detected negatively correlated with overall survival (log-rank, P<0.05). CONCLUSIONS: In conclusion, our study identified promising lncRNAs, which might be potential diagnostic biomarker and therapeutic targets and contribute to further understanding of the ceRNA pathogenesis in GC and guide for further investigation.