Identification of target and pathway of aspirin combined with Lipitor treatment in prostate cancer through integrated bioinformatics analysis

Our previous studies have confirmed that aspirin combined with Lipitor inhibited the development of prostate cancer (PCa), but the mechanisms need to be comprehensively expounded. The study aims to screen out the hub genes of combination therapy and to explore their association with the pathogenesis and prognosis of PCa. Gene expressions were quantified by RNA sequencing (RNA-seq). Altered biological function, pathways of differentially expressed genes (DEGs), protein-protein interaction network, the filtering of hub genes, gene co-expression and the pathogenesis and prognosis were revealed by bioinformatics analysis. The correlation between hub gene expression and patient survival was validated by Kaplan-Meier. The effects of silent DNA replication and sister chromatid cohesion 1 (siDSCC1) combined with Lipitor and aspirin on DSCC1 expression, viability, invasion and migration of PCa cells were detected by qRT-PCR, Wound healing and transwell assays. 157 overlapped DEGs involved in FoxO, PI3K-Akt and p53 signaling pathways were identified. Ten hub genes (NEIL3, CDC7, DSCC1, CDC25C, PRIM1, MCM10, FBXO5, DTL, SERPINE1, EXO1) were verified to be correlated with the pathology and prognosis of PCa. DSCC1 silencing not only inhibited the viability, migration and invasion of PCa cells, but also strengthened the suppressing effects of Lipitor and aspirin alone or in combination on PCa cells. The enrichment pathways and targets of Lipitor combined with aspirin in PCa are discovered, and DSCC1 silencing can potentiate the effect of Lipitor combined with aspirin in the treatment of PCa. •Differentially expressed genes are related to FoxO, PI3K-Akt and p53 signaling pathway.•The high expression of DSCC1, PRIM1, FBXO5 is related to the poor prognosis of prostate cancer.•SiDSCC1 can strengthen the inhibitory effects of Lipitor and aspirin on the viability, migration and invasion of PCa cells.