Prostate cancer is among the four most diagnosed cancers worldwide and it is the most common cause of death in men above the age of 60 in New Zealand. Zinc levels play an important role in normal prostate cells and possibly prostate cancer development due to the fact that the metabolism of prostate glands is mainly based on zinc. It also is a co-factor for many proteins, of which the most prominent one is transcription factor p53. Zinc therefore has an important role in other cell processes. Recently, studies have indicated that patients diagnosed with prostate cancer have elevated levels of urate. This study is attempting to understand the implications of these elevated urate levels on prostate cancer development and to identify the urate transporter involved in these processes. Based on our gene array analysis we examined the regulation of two zinc transporters by urate, namely ZIP1 and ZIP3, in the normal prostate cell line PNT1A and in three prostate cancer cell lines LNCaP, DU145 and PC-3. ZIP1 mRNA and protein expression increased in PNT1A and PC-3 cells upon urate treatment, while they decreased in LNCaP cells and didn’t change in DU145 cells. ZIP3 mRNA and protein expression was elevated in PNT1A cells in the presence of 500 µM of urate, but only protein levels were significantly reduced in DU145 and PC-3 cells. Similar to ZIP1 mRNA levels of ZIP3 were down-regulated in LNCaP cells after urate treatment. These results indicate that hyperuricemia has a significant impact on ZIP1 and ZIP3 expression in different stages of prostate cancer and especially in the non-aggressive stages, suggesting that urate may be involved in initial stages of cancer development. Using array analysis and real-time PCR, we were able to delineate the impact of urate on several miRNAs, especially miR-34a, which we have identified as a possible regulator for ZIP3. Exposure to high urate concentrations has significantly down-regulated miR-34a in all prostate cancer cell lines indicating that regulation of miR-34a may be the key mechanism to induce the transition from a normal prostate epithelial cell to a malignant proliferating and metastasising cell. We have identified other miRNAs such as miR-21, miR-106, miR-125 and miR-331, which are vital for the cell cycle and which are up-regulated by high urate plasma levels as well as miR-126 that is down-regulated by hyperuricemic conditions. Two of these, miR-21 and miR-126, are putative regulators of drug and zinc transporters. Further analysis of transporters facilitating the urate effect on prostate cancer cells identified GLUT9, which is known as the major renal urate transporter, as the main candidate. Investigations on primary prostate epithelial cells are underway to prove that high plasma urate levels contribute to the development of prostate cancer by regulating the p53/miR-34a pathway as well as zinc homeostasis, which are or are becoming the hallmarks of cancer.