Prostate cancer (PCa) is the third most common malignancy worldwide. Novel and effective therapeutic targets are needed for PCa. The purpose of this study was to discover novel therapeutic targets for PCa by performing advanced analysis on PCa RNA sequencing (RNAseq) data from The Cancer Genome Atlas (TCGA). Weighted correlation-network analysis (WGCNA) was performed on the RNAseq data of tumor samples, and the module most relevant to the Gleason score was identified. Combining differential gene-expression analysis and survival analysis, we narrowed down potential therapeutic target genes and found that PKMYT1 might be one. Subsequently, functional studies (i.e., cell-proliferation assays, cell cycle analysis, and colony-formation assays) demonstrated that knockdown of PKMYT1 significantly inhibited the growth of PCa cells. Further investigation illustrated that PKMYT1 promoted the growth of PCa cells through targeting CCNB1 and CCNE1 expression. In addition, fostamatinib, an inhibitor of PKMYT1, effectively inhibited the proliferation of PCa cells. Taken together, our results suggest that PKMYT1 is a gene associated with malignancy of PCa and is a novel therapeutic target.
Keywords: Fostamatinib; Gleason score; PKMYT1; Prostate cancer; Weighted correlation-network analysis.
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