Human-like hyperplastic prostate with low ZIP1 induced solely by Zn deficiency in rats

Significance Prostate cancer in man is associated with Zn loss, citrate metabolite reduction, overexpression of the miR-183-96-182 cluster, and regulation of Zn homeostasis through Zn transporter suppression. Our mechanistic study shows that a low-Zn diet upregulates this miR cluster in Zn-deficient middle-aged rat prostate, with ZIP1 mRNA/protein downregulation and a citrate-oxidizing metabolic phenotype, linking citrate reduction directly to prostatic Zn loss. The findings of this study show that the transcriptional and metabolic signal pathways induced by Zn deficiency in rats and almost certainly in men are critical for the development of human and rat prostate cancer and provide a strong rationale for including Zn supplementation in clinical trials to reduce the prostate cancer burden in the human population.