title: Oncogenic miRNA-182-5p targets Smad4 and RECK in human bladder cancer.
abstract: Onco-miR-182-5p has been reported to be over-expressed in bladder cancer (BC) tissues however a detailed functional analysis of miR-182-5p has not been carried out in BC. Therefore the purpose of this study was to: 1. conduct a functional analysis of miR-182-5p in bladder cancer, 2. assess its usefulness as a tumor marker, 3. identify miR-182-5p target genes in BC. Initially we found that miR-182-5p expression was significantly higher in bladder cancer compared to normal tissues and high miR-182-5p expression was associated with shorter overall survival in BC patients. To study the functional significance of miR-182-5p, we over-expressed miR-182-5p with miR-182-5p precursor and observed that cell proliferation, migration and invasion abilities were increased in BC cells. However cell apoptosis was inhibited by miR-182-5p. We also identified Smad4 and RECK as potential target genes of miR-182-5p using several algorithms. 3'UTR luciferase activity of these target genes was significantly decreased and protein expression of these target genes was significantly up-regulated in miR-182-5p inhibitor transfected bladder cancer cells. MiR-182-5p also increased nuclear beta-catenin expression and while Smad4 repressed nuclear beta-catenin expression. In conclusion, our data suggests that miR-182-5p plays an important role as an oncogene by knocking down RECK and Smad4, resulting in activation of the Wnt-beta-catenin signaling pathway in bladder cancer.
authors.affiliation: Department of Urology, San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hirata
authors.forename: Koji
authors.initials: K
authors.lastname: Ueno
authors.forename: Varahram
authors.initials: V
authors.lastname: Shahryari
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Z Laura
authors.initials: ZL
authors.lastname: Tabatabai
authors.forename: Yuji
authors.initials: Y
authors.lastname: Hinoda
authors.forename: Rajvir
authors.initials: R
authors.lastname: Dahiya
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D001483:Base Sequence; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival / Q000235:genetics; D058851:GPI-Linked Proteins / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009857:Oncogenes / Q000235:genetics*; D051901:Smad4 Protein / Q000378:metabolism*; D016019:Survival Analysis; D014162:Transfection; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology; D051176:beta Catenin / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D058851:GPI-Linked Proteins; D035683:MicroRNAs; C538984:Mirn182 microRNA, human; C115460:RECK protein, human; C497796:SMAD4 protein, human; D051901:Smad4 Protein; D051176:beta Catenin; D008156:Luciferases