The miR-183 family cluster alters zinc homeostasis in benign prostate cells, organoids and prostate cancer xenografts

Scientific reports

Authors: Dambal, Shweta; Baumann, Bethany; McCray, Tara; Williams, LaTanya; Richards, Zachary; Deaton, Ryan; Prins, Gail S; Nonn, Larisa;
PDF

Publisher: Nature Publishing Group

Abstract

The miR-183 cluster, which is comprised of paralogous miRs-183, -96 and -182, is overexpressed inmany cancers, including prostate adenocarcinoma (PCa). Prior studies showed that overexpression ofindividual pre-miRs-182, -96 and -183 in prostate cells decreased zinc import, which is a characteristic feature of PCa tumours. Zinc is concentrated in healthy prostate 10-fold higher than any other tissue, and an >80% decrease in zinc is observed in PCa specimens. Here, we studied the effect of overexpression of the entire 4.8 kb miR-183 family cluster, including the intergenic region which contains highly conserved genomic regions, in prostate cells. This resulted in overexpression of mature miR-183 family miRs at levels that mimic cancer-related changes. Overexpression of the miR-183 cluster reduced zinc transporter and intracellular zinc levels in benign prostate cells, PCa xenografts and fresh prostate epithelial organoids. Microarray analysis of miR-183 family cluster overexpression in prostate cells showed an enrichment for cancer-related pathways including adhesion, migration and wound healing. An active secondary transcription start site was identified within the intergenic region of the miR-183 cluster, which may regulate expression of miR-182. Taken together, this study shows that physiologically relevant expression of the miR-183 family regulates zinc levels and carcinogenic pathways in prostate cells.

We use cookies to understand how you use our site and to improve the overall user experience. This includes personalizing content and advertising. Read our Privacy Policy