miR-145 suppress the androgen receptor in prostate cancer cells and correlates to prostate cancer prognosis.
Författare
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.
Avdelning/ar
- Medicinsk molekylärbiologi
- Klinisk kemi, Malmö
- Avdelningen för translationell cancerforskning
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
- Urologisk cancerforskning, Malmö
- EpiHealth: Epidemiology for Health
Publiceringsår
2015
Språk
Engelska
Sidor
858-866
Publikation/Tidskrift/Serie
Carcinogenesis
Volym
36
Issue
8
Fulltext
- Available as PDF - 12 MB
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Länkar
Dokumenttyp
Artikel i tidskrift
Förlag
Oxford University Press
Ämne
- Cancer and Oncology
Status
Published
Forskningsgrupp
- Medical Molecular Biology
- Clinical Chemistry, Malmö
- Urological cancer, Malmö
ISBN/ISSN/Övrigt
- ISSN: 0143-3334