title: Oncogenic Activity of miR-650 in Prostate Cancer Is Mediated by Suppression of CSR1 Expression.
abstract: Cellular stress response 1 (CSR1) is a tumor suppressor gene whose expression was frequently down-regulated in prostate cancer. The mechanism of its down-regulation, however, is not clear. Here, we show that the 3' untranslated region of CSR1 contains a target site of miR-650. High level of miR-650 was found in prostate cancer samples and cell lines. Degradation of miR-650 by specific inhibitor dramatically increased the expression levels of CSR1. Interaction between miR-650 and its target site in the 3' untranslated region was validated through luciferase reporter system. Mutation at the target site completely abrogated the activity of miR-650 on the 3' untranslated region of CSR1. Inhibition of miR-650 reversed the expression suppression of CSR1, suppressed colony formation, and blocked cell cycle entry to the S phase of both PC3 and DU145 cells. Animal model showed significant decrease of tumor volume, rate of metastasis, and mortality of severe combined immunodeficient mice xenografted with PC3 or DU145 cells transformed with inhibitor of miR-650. Our analyses demonstrate that suppression of CSR1 expression is a novel mechanism critical for the oncogenic activity of miR-650.
authors.affiliation: Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Ze-Hua
authors.initials: ZH
authors.lastname: Zuo
authors.affiliation: Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Yan P
authors.initials: YP
authors.lastname: Yu
authors.affiliation: Department of Biostatistics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Biostatistics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Silvia
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Amantha
authors.initials: A
authors.lastname: Martin
authors.affiliation: Department of Biostatistics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: George
authors.initials: G
authors.lastname: Tseng
authors.affiliation: Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. Electronic address: luoj@msx.upmc.edu.
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Luo
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000368:Aged; D000595:Amino Acid Sequence; D000818:Animals; D063646:Carcinogenesis / Q000235:genetics; D045744:Cell Line, Tumor; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006360:Heat-Shock Proteins / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D020871:RNA Stability; D011817:Rabbits; D051117:Scavenger Receptors, Class A / Q000235:genetics* / Q000276:immunology; D046888:Tissue Array Analysis; D015854:Up-Regulation
chemical_list: D020413:3' Untranslated Regions; D006360:Heat-Shock Proteins; C550124:MIRN650 microRNA, human; D035683:MicroRNAs; C112525:SCARA3 protein, human; D051117:Scavenger Receptors, Class A