Increasing evidence showed that Cadmium (Cd) can accumulate in the body and damage cells, resulting in cancerigenesis of the prostate with complex mechanisms. In the present study, we aimed to explore the possible key genes, pathways and therapeutic drugs using bioinformatics methods. Microarray-based data were retrieved and analyzed to screen differentially expressed genes (DEGs) between Cd-treated prostate cells and controls. Then, functions of the DEGs were annotated and hub genes were screened. Next, key genes were selected from the hub genes via validation in a prostate cancer cohort from The Cancer Genome Atlas (TCGA). Afterward, potential drugs were further predicted. Consequently, a gene expression profile, GSE9951, was retrieved. Then, 361 up-regulated and 30 down-regulated DEGs were screened out, which were enriched in various pathways. Among the DEGs, seven hub genes (HSPA5, HSP90AB1, RHOA, HSPD1, MAD2L1, SKP2, and CCT2) were dysregulated in prostate cancer compared to normal controls, and two of them (HSPD1 and CCT2) might influence the prostate cancer prognosis. Lastly, ionomycin was predicted to be a potential agent reversing Cd-induced prostate cell malignant transformation. In summary, the present study provided novel evidence regarding the mechanisms of Cd-induced prostate cell malignant transformation, and identified ionomycin as a potential small molecule against Cd toxicity.

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http://dx.doi.org/10.1016/j.etap.2019.03.014DOI Listing

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