The miR-183 family cluster alters zinc homeostasis in benign prostate cells, organoids and prostate cancer xenografts.-猫眼课题宝

DOI：

10.1038/s41598-017-07979-y

发表时间：

2017-08-09

期刊：

Scientific reports

影响因子：

4.6

通讯作者：

中科院分区：

综合性期刊3区

文献类型：

作者：

Dambal S;Baumann B;McCray T;Williams L;Richards Z;Deaton R;Prins GS;Nonn L

来源链接：

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5550464/

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.