Identification of a Novel Prognosis-Associated ceRNA Network in Lung Adenocarcinoma via Bioinformatics analysis

Abstract

\n Backgroud: Long noncoding RNAs (lncRNAs) play an important role in the occurrence and development of lung adenocarcinoma (LUAD). The purpose of this study was to identify novel abnormally regulated lncRNA-microRNA (miRNA)-messenger RNA (mRNA) competing endogenous RNA (ceRNA) networks related to LUAD prognosis.Methods: We programmed an Agilent Microarray Scanner to screen for differentially expressed (DE) lncRNAs and mRNAs in 4 paired LUAD samples. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to annotate the DE lncRNAs and mRNAs. R bioinformatics packages, The Cancer Genome Atlas (TCGA) LUAD database and a Kaplan-Meier (KM) survival analysis tools were used to validate the microarray data and construct the lncRNA-miRNA-mRNA ceRNA regulatory network. Then, quantitative real-time PCR was used to validate the DE lncRNAs in 7 LUAD cell lines.Results: A total of 2819 DE lncRNAs and 2396 DE mRNAs (P-value < 0.05 and fold change ≥2 or ≤0.5) were identified in 4 paired LUAD tissue samples. In total, 255 of these DE lncRNAs were also identified in TCGA. The GO and KEGG analysis results suggested that the DE genes were most enriched in angiogenesis and cell proliferation and closely related to human cancers. Moreover, the differential expression of ENST00000609697, ENST00000602992, and NR_024321 was consistent with the microarray data, as determined by quantitative real-time PCR validation in 7 LUAD cell lines, but only ENST00000609697 was associated with the overall survival of LUAD patients (log-rank P=0.029). Finally, through analysis of ENST00000609697 target genes, we identified the ENST00000609697–hsa-miR-6791-5p–RASL12 ceRNA network, which may play a tumor-suppressive role in LUAD.Conclusion: ENST00000609697 was abnormally expressed in LUAD. Furthermore, downregulation of ENST00000609697 and its target gene RASL12 were associated with poor prognosis in LUAD. The ENST00000609697–hsa-miR-6791-5p–RASL12 axis may play a tumor-suppressive role. These results may suggest new prognostic and therapeutic biomarkers for LUAD.