title: Regulatory Role of mir-203 in Prostate Cancer Progression and Metastasis.
abstract: OBJECTIVE
  Advanced metastatic prostate cancer (PCa) is a fatal disease, with only palliative therapeutic options. Though almost 80% of cases of metastatic PCa present bone metastasis, our current understanding of the molecular mechanisms that govern this metastatic dissemination remains fragmentary. The main objective of the present study was to identify microRNA (miRNA) genes that regulate metastatic PCa.
  
  
  METHODS
  miRNA expression profiling was done in human prostate cell lines to identify dysregulated miRNA components of advanced PCa. miR-203 expression was assessed in prostate carcinoma cell lines and clinical specimens by real-time PCR and in situ hybridization. To assess the biological significance of miR-203, miR-203 was reexpressed in bone metastatic PCa cell lines followed by in vitro and in vivo functional assays.
  
  
  RESULTS
  miR-203 expression is specifically attenuated in bone metastatic PCa suggesting a fundamental antimetastatic role for this miRNA. Reintroduction of miR-203 in bone metastatic PCa cell lines suppresses metastasis via inhibition of several critical steps of the metastatic cascade including epithelial-mesenchymal transition, invasion, and motility. Ectopic miR-203 significantly attenuated the development of metastasis in a bone metastatic model of PCa. Importantly, miR-203 regulates a cohort of pro-metastatic genes including ZEB2, Bmi, survivin, and bone-specific effectors including Runx2, a master regulator of bone metastasis.
  
  
  CONCLUSIONS
  miR-203 is an "antimetastatic" miRNA in PCa that acts at multiple steps of the PCa metastatic cascade via repression of a cohort of prometastatic targets. miR-203 may be an attractive target for therapeutic intervention in advanced PCa.
authors.affiliation: Department of Urology, Veterans Affairs Medical Center and University of California, San Francisco, California 94121, USA.
authors.forename: Sharanjot
authors.initials: S
authors.lastname: Saini
authors.forename: Shahana
authors.initials: S
authors.lastname: Majid
authors.forename: Soichiro
authors.initials: S
authors.lastname: Yamamura
authors.forename: Laura
authors.initials: L
authors.lastname: Tabatabai
authors.forename: Seong O
authors.initials: SO
authors.lastname: Suh
authors.forename: Varahram
authors.initials: V
authors.lastname: Shahryari
authors.forename: Yi
authors.initials: Y
authors.lastname: Chen
authors.forename: Guoren
authors.initials: G
authors.lastname: Deng
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Rajvir
authors.initials: R
authors.lastname: Dahiya
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017403:In Situ Hybridization; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008163:Luminescent Measurements / Q000379:methods; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D009368:Neoplasm Transplantation; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077022:Survivin; D014183:Transplantation, Heterologous
chemical_list: C107489:BIRC5 protein, human; D050659:Core Binding Factor Alpha 1 Subunit; D051034:Inhibitor of Apoptosis Proteins; C546703:MIRN203 microRNA, human; D035683:MicroRNAs; D000077022:Survivin; D008156:Luciferases