title: Heat-shock protein HSPB1 attenuates microRNA miR-1 expression thereby restoring oncogenic pathways in prostate cancer cells.
abstract: BACKGROUND
  Heat-shock proteins (HSPs) as well as microRNAs have been identified to orchestrate crucial mechanisms in prostate cancer (PCa) progression and treatment resistance. Due to cytoprotective properties of HSPB1 we analyzed molecular mechanisms of drug resistance in PCa cell culture systems, and notably found HSPB1 functionality linked to microRNA miR-1 activities.
  
  
  METHODS
  HSPB1 and miR-1 levels were genetically modified in PCa cell lines and alterations in molecular and cellular responses were assessed by quantitative reverse transcription/polymerase chain reaction, western blotting, and proliferation assays.
  
  
  RESULTS
  Our data provided for the first time evidence that HSPB1 regulates miR-1 expression, and subsequently restores oncogenic signaling pathways of androgen receptor (AR) and transforming growth factor β1 (TGFB1).
  
  
  CONCLUSIONS
  Our data point towards HSPB1 and miR-1 involvement in development of castration-resistant PCa and therefore represent promising targets for anticancer therapy of advanced PCa.
authors: Department of Urology, University Medicine Greifswald, Greifswald, Germany matthias.stope@uni-greifswald.de.
authors: Matthias B
authors: MB
authors: Stope
authors: Department of Urology, University Medicine Greifswald, Greifswald, Germany.
authors: Christian
authors: C
authors: Stender
authors: Department of Urology, University Medicine Greifswald, Greifswald, Germany.
authors: Tina
authors: T
authors: Schubert
authors: Department of Urology, University Medicine Greifswald, Greifswald, Germany.
authors: Stefanie
authors: S
authors: Peters
authors: Department of Urology, University Medicine Greifswald, Greifswald, Germany.
authors: Martin
authors: M
authors: Weiss
authors: Department of Oncology, Hematology and Stem Cell Transplantation, University Hospital Aachen, RWTH Aachen University, Aachen, Germany.
authors: Patrick
authors: P
authors: Ziegler
authors: Department of Urology, University Medicine Greifswald, Greifswald, Germany.
authors: Uwe
authors: U
authors: Zimmermann
authors: Department of Medical Biochemistry and Molecular Biology, University Medicine Greifswald, Greifswald, Germany.
authors: Reinhard
authors: R
authors: Walther
authors: Department of Urology, University Medicine Greifswald, Greifswald, Germany.
authors: Martin
authors: M
authors: Burchardt
mesh_terms: D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D018450:Disease Progression; D055551:HSP27 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006360:Heat-Shock Proteins; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D018832:Molecular Chaperones; D064129:Prostatic Neoplasms, Castration-Resistant / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011944:Receptors, Androgen / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; C544547:MIRN1 microRNA, human; D035683:MicroRNAs; D018832:Molecular Chaperones; D011944:Receptors, Androgen; D053773:Transforming Growth Factor beta1
keywords: Prostate cancer; heat-shock protein HSPB1; microRNA miR-1; oncogenesis