title: miR-183-96-182 cluster is overexpressed in prostate tissue and regulates zinc homeostasis in prostate cells.
abstract: Decreased zinc levels are a hallmark of prostate cancer tumors as zinc uniquely concentrates in healthy prostate tissue. Increased dietary zinc correlates with decreased risk of advanced prostate cancer and decreased mortality from prostate cancer. The mechanisms of prostatic zinc homeostasis are not known. Lower zinc levels in the tumor are correlated directly with decreased expression of the zinc transporter hZIP1. We report identification of a microRNA cluster that regulates multiple zinc transporters, including hZIP1. Screening in laser capture microdissected prostate cancer tumors identified miR-182 as a potential regulator of hZIP1. Regulation of hZIP1 by miR-182 via two binding sites was confirmed in primary prostate cell cultures. miR-96 and miR-183 are expressed as a cluster with miR-182 and share similar sequences. Array profiling of tissue showed that miR-183, -96, and -182 are higher in prostate cancer tissue compared with normal prostate. Overexpression of the entire miR-183-96-182 cluster suppressed five additional zinc transporters. Overexpression of miR-183, -96, and -182 individually or as a cluster diminished labile zinc pools and reduced zinc uptake, demonstrating this miR cluster as a regulator of zinc homeostasis. We observed regulation of zinc homeostasis by this cluster in prostate cells and HEK-293 cells, suggesting a universal mechanism that is not prostate-specific. To our knowledge, this is the first report of a miR cluster targeting a family of metal transport proteins. Individually or as a cluster, miR-183, -96, and -182 are overexpressed in other cancers too, implicating this miR cluster in carcinogenesis.
authors: Department of Pathology, University of Illinois, Chicago, Illinois 60612, USA.
authors: Brittany L
authors: BL
authors: Mihelich
authors: Ekaterina A
authors: EA
authors: Khramtsova
authors: Nicole
authors: N
authors: Arva
authors: Avani
authors: A
authors: Vaishnav
authors: Daniel N
authors: DN
authors: Johnson
authors: Angeline A
authors: AA
authors: Giangreco
authors: Elena
authors: E
authors: Martens-Uzunova
authors: Omar
authors: O
authors: Bagasra
authors: André
authors: A
authors: Kajdacsy-Balla
authors: Larisa
authors: L
authors: Nonn
mesh_terms: D027682:Cation Transport Proteins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D057809:HEK293 Cells; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis*; D005810:Multigene Family / Q000502:physiology*; D011467:Prostate / Q000166:cytology / Q000378:metabolism*; D020218:Response Elements / Q000502:physiology; D015032:Zinc / Q000378:metabolism*
chemical_list: D027682:Cation Transport Proteins; C533449:MIRN183 microRNA, human; C541492:MIRN96 microRNA, human; D035683:MicroRNAs; C538984:Mirn182 microRNA, human; C403517:SLC39A1 protein, human; D015032:Zinc