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miR-205 negatively regulates the androgen receptor and is associated with adverse outcome of prostate cancer patients.

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Author

Summary, in English

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.Conclusion:Taken together, these findings imply that miR-205 might have therapeutic potential, especially for the castration resistant and currently untreatable form of PCa.British Journal of Cancer advance online publication, 9 April 2013; doi:10.1038/bjc.2013.131 www.bjcancer.com.

Department/s

Publishing year

2013

Language

English

Pages

1668-1676

Publication/Series

British Journal of Cancer

Volume

108

Issue

8

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Cancer and Oncology

Status

Published

Research group

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

ISBN/ISSN/Other

  • ISSN: 1532-1827