Identification of lncRNA-associated competing endogenous RNA networks for occurrence and prognosis of gastric carcinoma

Abstract

Background: Gastric cancer (GC) is one of the common digestive malignancies worldwide and causes a severe public health issue. So far, the underlying mechanisms of GC are largely unclear. Thus, our aim is to identify the long non-coding RNA (lncRNA) associated competing endogenous RNA (ceRNA) specialized for occurrence and progression in GC.Methods: The comprehensive online dataset, TCGA, was downloaded and used for identification of differentially expressed (DE) lncRNA, miRNA and mRNA screen with the value of logFC = 1 and FDR < 0.05, respectively. The interactions between lncRNA and miRNA as well mRNA and miRNA were predicted via multiple online databases, such as miRcode and Targetscan. Then the ceRNA network was constructed accompanied with gene set enrichment analysis and survival analysis. In addition, RT-qPCR and in vitro assay was carried out to validate the effect of the hub lncRNAs.Results: We identified 1485 lncRNAs, 312 miRNAs and 4260 mRNAs were differentially expressed between GC and normal tissues, respectively. Then, we generated a ceRNA network with 909 edges and 253 nodes including 76 lncRNA, 18 miRNA and 159 mRNA. This ceRNA network was involved in MET activates PTK2 signalling, MET promotes cell motility and non-integrin membrane-ECM interactions. Next, by univariate and multivariate analysis, there were 9 hub lncRNAs emerged and were associated subnetwork involved in actin filament binding and MAPK signaling pathway. The in vitro assay indicated lncRNA INHBA-AS1 and CCDC144NL-AS1 may positively related to the GC aggressive features, including proliferation, invasion and migration.Conclusion: In summary, we constructed a ceRNA network involved in the GC development. Moreover, we also identified 9 hub lncRNA-associated network related to prognosis of GC and validated two out of them as promising oncogenes. This may provide potential biomarkers or therapeutic target for GC in future.