The miR-183 family cluster alters zinc homeostasis in benign prostate cells, organoids and prostate cancer xenografts
Year: 2017
Type: article
Abstract: The miR-183 cluster, which is comprised of paralogous miRs-183, -96 and -182, is overexpressed in many cancers, including prostate adenocarcinoma (PCa). Prior studies showed that overexpression of individual 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.
Source: Scientific Reports
Institution: University of Illinois Chicago
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,690
Awards: G102163711, G107546177, G1313983767, G1505794299, G1664757510, G2101401529, G2287611682, G262962599, G2887060908, G3075337988, G340565428, G498139845, G5106849484, Estrogen Receptors in Human Prostate Stem-Progenitor Cells, G5607048534, Effects of Arsenic on Human Prostate Stem Cells and Prostate Cancer Risk, MiR-183-96-182 cluster, prostatic zinc homeostasis and carcinogenesis, G6848031779, G6918803902, G7368700025, G969889393, G993149817
OpenAlex ID: W2743560149