title: MiR-182 Is Associated with Growth, Migration and Invasion in Prostate Cancer via Suppression of FOXO1.
abstract: BACKGROUND
  MicroRNA (miRNA) have been shown to regulate gene expression in many cancers. MiR-182 has recently been found to be prognostic for patients treated with radical prostatectomy for prostate cancer. We sought to assess miR-182 as a prognostic marker and understand its role in prostate cancer progression and metastasis.
  
  
  METHODS
  We analysed miR-182 expression among 147 men treated for prostate cancer using biochemical recurrence and metastasis as the endpoints. We examined miR-182 expression in prostate cancer cells and created cell lines that overexpressed miR-182 for functional assays. Finally, we examined pathways through which miR-182 may function using prediction algorithms and confirmed by Western blotting and knock-down assays.
  
  
  RESULTS
  We found that miR-182 was not associated with biochemical recurrence (p=0.1111) or metastasis (p=0.9268) following radical prostatectomy. However, in mechanistic assays, we found that miR-182 expression was higher among aggressive prostate cancer cells and that ectopic miR-182 expression resulted in increased proliferation, migration and invasion in vitro. We identified FOXO1 as regulated by miR-182 in prostate cancer cells, confirmed that ectopic miR-182 expression resulted in diminished FOXO1 levels, and showed that miR-182 inhibition results in increased FOXO1 levels. Expression of FOXO1 (p=0.0014) in tumors from patients who developed biochemical recurrence compared to tumors from patients who were recurrence-free five years after their radical prostatectomy.
  
  
  CONCLUSIONS
  Our findings suggest that miR-182 may act to increase prostate cancer proliferation, migration and invasion through suppression of FOXO1. This may be valuable in the development of further therapeutic interventions.
authors.affiliation: 1. Division of Urology, Sunnybrook Health Sciences Centre, Toronto, Ontario.
authors.forename: Christopher J D
authors.initials: CJ
authors.lastname: Wallis
authors.affiliation: 2. Department of Pathobiology and Laboratory Medicine, University of Toronto.
authors.forename: Aida
authors.initials: A
authors.lastname: Gordanpour
authors.affiliation: 1. Division of Urology, Sunnybrook Health Sciences Centre, Toronto, Ontario.
authors.forename: Jessica Stojcic
authors.initials: JS
authors.lastname: Bendavid
authors.affiliation: 3. Department of Pathology, Sunnybrook Health Sciences Centre. Toronto, Ontario, Canada.
authors.forename: Linda
authors.initials: L
authors.lastname: Sugar
authors.affiliation: 1. Division of Urology, Sunnybrook Health Sciences Centre, Toronto, Ontario.
authors.forename: Robert K
authors.initials: RK
authors.lastname: Nam
authors.affiliation: 2. Department of Pathobiology and Laboratory Medicine, University of Toronto ; 3. Department of Pathology, Sunnybrook Health Sciences Centre. Toronto, Ontario, Canada ; 4. Biological Sciences, Sunnybrook Research Institute, Toronto, Ontario, Canada.
authors.forename: Arun
authors.initials: A
authors.lastname: Seth
keywords: MicroRNA; prostatectomy.; prostatic neoplasms