Integrated Analysis of a ceRNA (lncRNA-miRNA-mRNA) Regulatory Network for Prostate Cancer

Abstract

Objective. This study was to construct a ceRNA (lncRNA-miRNA-mRNA) regulatory network for prostate cancer (PCa) and to explore the prognostic correlation, key biological functions, and pathways of core RNAs. Methods. Three subgene expression matrices (miRNA, lncRNA, and mRNA expression matrix) were taken from the TCGA database and used in this investigation. Differential expression analysis and differential expression miRNAs were carried out. Next, the ceRNA (lncRNA-miRNA-mRNA) regulatory complex was used to visualize our data and show how they interacted. Ultimately, the primary molecular roles and biological pathways of PCa were identified using enrichment analysis by the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO). An effect of AC016773.1 on prostate cancer cell proliferation was investigated by knocking out AC016773.1 in an animal model. The interrelationship between AC016773.1 and hsa-mir-25 was validated using RNA immunoprecipitation technology. Results. The lncRNA, miRNA, and mRNA expression matrices obtained from the TCGA database contain 16901, 1881, and 19962 transcripts, respectively. Through differential expression analysis, we obtained 2010 de lncRNA comparative information, 75 lncRNA and miRNA interaction pairs, and 31 targeted de mRNAs. Through the differential expression analysis of RNA nodes in the ceRNA regulatory network, we found that compared with the NP group, in the PCa group, there were 14 lncRNAs upregulated and 25 lncRNAs downregulated, 1 miRNA upregulated and 3 miRNA downregulated, and 10 mRNA upregulated and 21 mRNA downregulated. In KEGG enrichment analysis, the pathways identified by targeted DE-mRNAs were mainly related to calcium signaling pathway, EGFR tyrosine kinase inhibitor resistance, melanoma, PI3K−Akt signaling pathway, and proteoglycans in cancer. In animal models, it was found that knocking down AC016773.1 significantly reduced tumor volume and weight, indicating that AC016773.1 may promote the proliferation of PCa cells. The use of RNA immunoprecipitation technology indicates a direct binding between AC016773.1 and hsa-mir-25. Conclusion. We elucidated the network regulatory relationship of lncRNA-miRNA-mRNA in PCa and further explored the key molecular functions, biological pathways, and prognostic value of targeted DE-mRNAs.