The miR-183 family cluster alters zinc homeostasis in benign prostate cells, organoids and prostate cancer xenografts
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 char...
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2017
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oai:doaj.org-article:96ffe93432e54d89a630744093f956642021-12-02T11:40:13ZThe miR-183 family cluster alters zinc homeostasis in benign prostate cells, organoids and prostate cancer xenografts10.1038/s41598-017-07979-y2045-2322https://doaj.org/article/96ffe93432e54d89a630744093f956642017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07979-yhttps://doaj.org/toc/2045-2322Abstract 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.Shweta DambalBethany BaumannTara McCrayLaTanya WilliamsZachary RichardsRyan DeatonGail S. PrinsLarisa NonnNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017) |
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Medicine R Science Q Shweta Dambal Bethany Baumann Tara McCray LaTanya Williams Zachary Richards Ryan Deaton Gail S. Prins Larisa Nonn The miR-183 family cluster alters zinc homeostasis in benign prostate cells, organoids and prostate cancer xenografts |
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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. |
format |
article |
author |
Shweta Dambal Bethany Baumann Tara McCray LaTanya Williams Zachary Richards Ryan Deaton Gail S. Prins Larisa Nonn |
author_facet |
Shweta Dambal Bethany Baumann Tara McCray LaTanya Williams Zachary Richards Ryan Deaton Gail S. Prins Larisa Nonn |
author_sort |
Shweta Dambal |
title |
The miR-183 family cluster alters zinc homeostasis in benign prostate cells, organoids and prostate cancer xenografts |
title_short |
The miR-183 family cluster alters zinc homeostasis in benign prostate cells, organoids and prostate cancer xenografts |
title_full |
The miR-183 family cluster alters zinc homeostasis in benign prostate cells, organoids and prostate cancer xenografts |
title_fullStr |
The miR-183 family cluster alters zinc homeostasis in benign prostate cells, organoids and prostate cancer xenografts |
title_full_unstemmed |
The miR-183 family cluster alters zinc homeostasis in benign prostate cells, organoids and prostate cancer xenografts |
title_sort |
mir-183 family cluster alters zinc homeostasis in benign prostate cells, organoids and prostate cancer xenografts |
publisher |
Nature Portfolio |
publishDate |
2017 |
url |
https://doaj.org/article/96ffe93432e54d89a630744093f95664 |
work_keys_str_mv |
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