Identification of a long non‑coding RNA‑mediated competitive endogenous RNA network in hepatocellular carcinoma.

The present study was designed to identify the endogenous RNA regulatory networks involved in hepatocellular carcinoma (HCC) by bioinformatic analysis. Both miRNA interaction network-based correlation analysis and expression-based Spearman correlation coefficients were utilized to identify potential mRNA-lncRNA interactions. Then, a competitive endogenous (ce)RNA network was constructed from these interactions, and network topology and Gene Ontology enrichment analyses were conducted to mine potential functions of ceRNAs. In HCC samples, a ceRNA network was constructed. It was composed of 35,657 edges connecting 113 lncRNAs and 6,136 mRNAs which were differentially expressed in HCC and normal liver tissues. Meanwhile, a number of significantly positively correlated mRNA and lncRNA pairs in this ceRNA network were found to be consistently positively correlated in another independent dataset. To be noted, further analyses on the potential roles of ceRNAs demonstrated than various lncRNAs such as LINC00657, TUG1 and SNHG1 may play key roles in HCC by regulating protein phosphorylation or cell cycle pathways or influencing miRNAs. From the perspective that lncRNAs can function as ceRNAs, this study revealed that the interaction between lncRNAs, miRNAs and mRNAs may provide new insight for the diagnosis and treatment in the tumorigenesis of hepatocellular carcinoma.