title: miR-205 negatively regulates the androgen receptor and is associated with adverse outcome of prostate cancer patients.
abstract: BACKGROUND
  The microRNA-205 (miR-205) has been shown to be deregulated in prostate cancer (PCa). Here we continue to investigate the prognostic and therapeutic potential of this microRNA.
  
  
  METHODS
  The expression of miR-205 is measured by qRT-PCR and in situ hybridisation in a well-documented PCa cohort. An AGO2-based RIP-Chip assay is used to identify targets that are verified with western blots, luciferase reporter assay, ELISA and immunohistochemistry.
  
  
  RESULTS
  The expression of miR-205 is inversely correlated to the occurrence of metastases and shortened overall survival, and is lower in castration-resistant PCa patients. The miR-205 expression is mainly localised to the basal cells of benign prostate tissues. Genes regulated by miR-205 are enriched in, for example, the MAPK/ERK, Toll-like receptor and IL-6 signaling pathways. We demonstrate binding of miR-205 to the 3'UTR of androgen receptor (AR) and decrease of both AR transcript and protein levels. This finding was corroborated in the patient cohort were miR-205 expression inversely correlated to AR immunostaining in malignant prostate cells and to serum levels of prostate-specific antigen, an androgen-regulated protein.
  
  
  CONCLUSIONS
  Taken together, these findings imply that miR-205 might have therapeutic potential, especially for the castration resistant and currently untreatable form of PCa.
authors.affiliation: Department of Laboratory Medicine, Division of Clinical Chemistry, Lund University, Malmö, Sweden.
authors.forename: Z
authors.initials: Z
authors.lastname: Hagman
authors.forename: B S
authors.initials: BS
authors.lastname: Haflidadóttir
authors.forename: J A
authors.initials: JA
authors.lastname: Ceder
authors.forename: O
authors.initials: O
authors.lastname: Larne
authors.forename: A
authors.initials: A
authors.lastname: Bjartell
authors.forename: H
authors.initials: H
authors.lastname: Lilja
authors.forename: A
authors.initials: A
authors.lastname: Edsjö
authors.forename: Y
authors.initials: Y
authors.lastname: Ceder
mesh_terms: D020413:3' Untranslated Regions; D002448:Cell Adhesion / Q000235:genetics; D045744:Cell Line, Tumor; D015331:Cohort Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D009362:Neoplasm Metastasis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; D011944:Receptors, Androgen; C534425:MIR205, human