Objective: To establish the competitive endogenous RNA (ceRNA) regulatory network related to phosphatase and tensin homologue (PTEN) in prostate cancer (PCa), and screen messenger RNA (mRNA), microRNA (miRNA) and long noncoding RNA (lncRNA) related to the prognosis of PCa to provide a theoretical basis for the diagnosis and prognosis of PCa.
Methods: Transcriptome data of 498 prostate cancer samples and 52 normal prostate samples were extracted in Cancer Genome Atlas (TCGA) database and differential expression (DE) lncRNAs, miRNA and mRNA were screened. The CytoHubba plug-in was used to identify the triple regulatory network of hub genes. On this basis, the PTEN-related ceRNA regulatory network was constructed. Kaplan-Meyer method was used to explore the related factors about the prognosis of PRAD patients. The gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) were performed to explore functional annotation and enrichment pathways.
Results: Amount to 1918 DElncRNAs, 68 DEmiRNAs and 2920 DEmRNAs were screened. And 8 lncRNAs, 7 miRNAs and 525 mRNAs were incorporated to build the lncRNA-miRNA-mRNA triple regulatory network by Cytoscape software. The enrichment analysis of GO and KEGG showed that these interaction proteins function mainly enriched in chemotaxis, urogenital system development and cell morphogenesis involved in differentiation. Three lncRNAs (MEG3, AGAP11, and ADAMTS9-AS2), five miRNAs (miR-93-3p, miR-141-3p, miR-222-3p, miR-590-3p and miR-3619-5a) and six mRNAs (NRG1, SHH, TIMP3, CLVS2, NFAT5 and ADAM22) were identified by the Cytoscape plug-in cytoHubba. Kaplan-Meier analysis screened out 2 DEmRNAs(NRG1 and CLVS2), 1 DElncRNAs(MEG3) and 1 DEmiRNA(miR-222-3p), which were associated with the prognosis of PRAD (P<0.05). Finally, we established a PTEN-related MEG3-hsa-miR-222-3p-NRG1/CLVS2 ceRNA network in PRAD. NRG1 and CLVS2 were related with methylation and immune infiltration in PRAD, which were high expressssion in PRAD by Immunohistochemical analysis.
Conclusion: In this study, the key RNAs related to PRAD prognosis are screened out by constructing the PTEN-related ceRNA regulatory network of PRAD, which provides a theoretical basis for the diagnosis and treatment of PRAD.