Heat-shock protein HSPB1 attenuates microRNA miR-1 expression thereby restoring oncogenic pathways in prostate cancer cells

Anticancer Res. 2014 Jul;34(7):3475-80.

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.

Materials and 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).

Conclusion: 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.

Keywords: Prostate cancer; heat-shock protein HSPB1; microRNA miR-1; oncogenesis.

MeSH terms

  • Cell Growth Processes / physiology
  • Cell Line, Tumor
  • Cloning, Molecular
  • Disease Progression
  • HSP27 Heat-Shock Proteins / genetics
  • HSP27 Heat-Shock Proteins / metabolism*
  • Heat-Shock Proteins
  • Humans
  • Male
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • Molecular Chaperones
  • Prostatic Neoplasms, Castration-Resistant / genetics
  • Prostatic Neoplasms, Castration-Resistant / metabolism*
  • Prostatic Neoplasms, Castration-Resistant / pathology
  • Receptors, Androgen / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Transforming Growth Factor beta1 / metabolism

Substances

  • HSP27 Heat-Shock Proteins
  • HSPB1 protein, human
  • Heat-Shock Proteins
  • MIRN1 microRNA, human
  • MicroRNAs
  • Molecular Chaperones
  • Receptors, Androgen
  • Transforming Growth Factor beta1