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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Autores principales: Shweta Dambal, Bethany Baumann, Tara McCray, LaTanya Williams, Zachary Richards, Ryan Deaton, Gail S. Prins, Larisa Nonn
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Publicado: Nature Portfolio 2017
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spelling 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)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle 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
description 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
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