Screening key miRNAs and genes in prostate cancer by microarray analysis

BACKGROUND: Prostate cancer (PCa) is the second most frequent cancer and the fifth leading cause of cancer-related death in men while the mechanisms remain unclear. METHODS: Differentially expressed mRNAs (DEmRNAs) and miRNAs (DEmiRNAs) between PCa and non-tumor controls were identified by using microarray analysis. Functional annotation of DEmRNAs, construction of protein-protein interaction (PPI) network and prediction of upstream transcription factors and downstream target DEmRNAs of DEmiRNAs were conducted to further research functions of key DEmRNAs and DEmiRNAs. Validation of selected DEmRNAs and survival analysis were conducted by using The Cancer Genome Atlas (TCGA). RESULTS: Total of 91 DEmRNAs and 62 DEmiRNAs were obtained. Thrombospondin-4 precursor (THBS4) was the most significantly up-regulated DEmRNA whose product was predicted to interact with the hub protein of the PCa-specific PPI network, collagen type I alpha 1 chain (COL1A1). Both ATP binding cassette subfamily C member 4 (ABCC4) and endothelin receptor type B (EDNRB) have great prognostic value for PCa. Thrombospondin type 1 domain containing 4 (THSD4) was a down-regulated DEmRNA regulated by several cancer-related miRNAs including has-miR-107, hsa-miR-3175 and hsa-miR-484. Two miRNAs (hsa-miR-428 and hsa-miR-4284) involve in PCa by regulating BMP5-BAMBI interaction and TGF-beta signaling pathway. The expression of selected DEmRNAs between PCa and non-tumor controls in TCGA was consistent with that in our microarray analysis, generally. CONCLUSIONS: Key DEmRNAs and DEmiRNAs between PCa and non-tumor controls were identified in this study which provided clues for exploring the molecular mechanism and developing potential biomarkers and therapeutic target sites for PCa.