miR-205 negatively regulates the androgen receptor and is associated with adverse outcome of prostate cancer patients.
Hagman Z., Haflidadóttir BS., Ceder JA., Larne O., Bjartell A., Lilja H., Edsjö A., Ceder Y.
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.