Journal
BRITISH JOURNAL OF CANCER
Volume 108, Issue 8, Pages 1668-1676Publisher
SPRINGERNATURE
DOI: 10.1038/bjc.2013.131
Keywords
miRNA; miR-205; prostate cancer; androgen receptor; CRPC; metastases
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Funding
- European Union [201438]
- Swedish Research council
- Gunnar Nilssons Cancer foundation
- Jeanssons foundation
- Gyllenstiernska Krapperups foundation
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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.
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