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miR-145 suppress the androgen receptor in prostate cancer cells and correlates to prostate cancer prognosis.

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Author

Summary, in English

Androgen signalling through the androgen receptor (AR) is essential for prostate cancer initiation, progression and transformation to the lethal castration-resistant state. The aim of this study was to characterize the mechanisms by which miR-145 deregulation contribute to prostate cancer progression. The miR-145 levels, measured by quantitative reverse transcription-polymerase chain reaction, were found to inversely correlate with occurrence of metastases, survival and androgen deprivation therapy response in a well-characterized prostate cancer cohort. Introduction of ectopic miR-145 in prostate cancer cells generated an inhibitory effect on the AR at both transcript and protein levels as well as its activity and downstream targets prostate-specific antigen (PSA), kallikrein-related peptidase 2 and TMPRSS2. The regulation was shown to be mediated by direct binding using Ago2-specific immunoprecipitation, but there was also indication of synergetic AR activation. These findings were verified in clinical prostate specimens by demonstrating inverse correlations between miR-145 and AR expression as well as serum PSA levels. In addition, miR-145 was found to regulate androgen-dependent cell growth in vitro. Our findings put forward novel possibilities of therapeutic intervention, as miR-145 potentially could decrease both the stem cells and the AR expressing bulk of the tumour and hence reduce the transformation to the deadly castration-resistant form of prostate cancer.

Publishing year

2015

Language

English

Pages

858-866

Publication/Series

Carcinogenesis

Volume

36

Issue

8

Document type

Journal article

Publisher

Oxford University Press

Topic

  • Cancer and Oncology

Status

Published

Research group

  • Medical Molecular Biology
  • Clinical Chemistry, Malmö
  • Urological cancer, Malmö

ISBN/ISSN/Other

  • ISSN: 0143-3334