Identification of miRNAs biomarkers for prostate cancer in serum and tissue based on bioinformatic analysis and experimental validation

Abstract

Abstract Purpose The aim of our research is to identify the key miRNAs and construct miRNA-mRNA networks for Prostate cancer (PCa). Methods Microarray dataset GSE112264 consisting of 1591 male serum samples and tissue miRNA data from TCGA including 497 prostate cancer and 52 normal sample were included for analysis. Differentially expressed miRNAs (DE-miRNAs) were detected by R package and miRTarBase was used to predict the common target genes. Then GO and KEGG pathway analysis was performed for the target genes. Protein–protein interaction (PPI) network which revealed top 10 hub genes was constructed by STRING database and Cytoscape software. The potential hub genes expression examined by UALCAN database. Finally, GSE112264, TCGA datasets and clinical samples were used for verifying the consistency of miRNAs expression in serum and tissue. Results A total of 948 target genes of the overlapped two downregulated miRNAs (miR-146a-3p and miR-136-3p) were predicted. Functional enrichment analysis indicated that significant DE-miRNAs were related to PCa-related pathway such as protein binding, mTOR signaling pathway and porphyrin and chlorophyll metabolism. 4 hub genes were identified from PPI network including NSF, HIST2H2BE, IGF2R and CADM1 and verified to be aberrantly expressed in UALCAN database. Experiment results indicated that only miR-136-3p was markedly reduced both in serum and tissue. Conclusion In this study, we established miRNA-mRNA network and provided new insight into the diagnostic biomarkers for PCa.