Identification and analysis of survival-associated ceRNA triplets in prostate adenocarcinoma

Prostate adenocarcinoma (PRAD) is one of the most common causes of cancer-associated mortality worldwide. Recent evidence has emphasized the role of competitive endogenous RNAs (ceRNA) in prostate cancer. However, the current understanding of the roles that ceRNAs play in survival-associated PRAD remains in its infancy. In the present study, a PRAD-specific ceRNA network was constructed by integrating long non-coding RNA (lncRNA)-microRNA (miRNA)-gene interactions using experimental and computational methods, as well as expression correlations from The Cancer Genome Atlas database. The topological features of the ceRNA network were then analyzed and the PRAD-risk lncRNAs were compared with non-risk lncRNAs within this network. It was revealed that PRAD-risk lncRNAs had a higher degree, closeness and betweenness centrality, but also had the shortest path length. Finally, 42 significant PRAD-survival-associated triplets were identified. Notably, these triplets may form a compacted subnetwork composed of only 25 nodes (5 miRNAs, 4 lncRNAs and 16 genes) and 32 edges, indicating that some nodes were involved in many triplets. Among this subnetwork, mir-21 indicated the highest degree centrality and was demonstrated to exert its oncogenic effects in prostate tumors by downregulating transforming growth factor β receptor 2 (TGFBR2). Two triplets (MIR22HG_hsa-mir-21_TGFBR2 and MIR22HG_hsa-mir-21_BCL2) were finally identified; not only were they significantly associated with PRAD survival but they also had the highest average degree in the identified subnetwork. The results from the present study provide further insights into the understanding of the potential roles and interactions of ceRNA triplets and potential prognosis markers for PRAD.