Construction and analysis of mRNA, miRNA, lncRNA, and TF regulatory networks reveal the key genes associated with prostate cancer.PLoS One. 2018; 13(8):e0198055.Plos
Prostate cancer (PCa) causes a common male urinary system malignant tumour, and the molecular mechanisms of PCa are related to the abnormal regulation of various signalling pathways. An increasing number of studies have suggested that mRNAs, miRNAs, lncRNAs, and TFs could play important roles in various biological processes that are associated with cancer pathogenesis. This study aims to reveal functional genes and investigate the underlying molecular mechanisms of PCa with bioinformatics.
Original gene expression profiles were obtained from the GSE64318 and GSE46602 datasets in the Gene Expression Omnibus (GEO). We conducted differential screens of the expression of genes (DEGs) between two groups using the online tool GEO2R based on the R software limma package. Interactions between differentially expressed miRNAs, mRNAs and lncRNAs were predicted and merged with the target genes. Co-expression of miRNAs, lncRNAs and mRNAs was selected to construct mRNA-miRNA-lncRNA interaction networks. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed for the DEGs. Protein-protein interaction (PPI) networks were constructed, and transcription factors were annotated. Expression of hub genes in the TCGA datasets was verified to improve the reliability of our analysis.
The results demonstrate that 60 miRNAs, 1578 mRNAs and 61 lncRNAs were differentially expressed in PCa. The mRNA-miRNA-lncRNA networks were composed of 5 miRNA nodes, 13 lncRNA nodes, and 45 mRNA nodes. The DEGs were mainly enriched in the nuclei and cytoplasm and were involved in the regulation of transcription, related to sequence-specific DNA binding, and participated in the regulation of the PI3K-Akt signalling pathway. These pathways are related to cancer and focal adhesion signalling pathways. Furthermore, we found that 5 miRNAs, 6 lncRNAs, 6 mRNAs and 2 TFs play important regulatory roles in the interaction network. The expression levels of EGFR, VEGFA, PIK3R1, DLG4, TGFBR1 and KIT were significantly different between PCa and normal prostate tissue.
Based on the current study, large-scale effects of interrelated mRNAs, miRNAs, lncRNAs, and TFs established a new prostate cancer network. In addition, we conducted functional module analysis within the network. In conclusion, this study provides new insight for exploration of the molecular mechanisms of PCa and valuable clues for further research into the process of tumourigenesis and its development in PCa.