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.

The MITF protein is a member of the MYC family of basic helix-loop-helix leucine zipper (bHLH-Zip) transcription factors and is most closely related to the TFE3, TFEC, and TFEB proteins. In the mouse, MITF is required for the development of several different cell types, including the retinal pigment epithelial (RPE) cells of the eye. In Mitf mutant mice, the presumptive RPE cells hyperproliferate, abnormally express the retinal transcriptional regulator Pax6, and form an ectopic neural retina. Here we report the structure of the Mitf gene in Drosophila and demonstrate expression during embryonic development and in the eyeantennal imaginal disc. In vitro, transcriptional regulation by Drosophila Mitf, like its mouse counterpart, is modified by the Eyeless (Drosophila Pax6) transcription factor. In vivo, targeted expression of wild-type or dominant-negative Drosophila Mitf results in developmental abnormalities reminiscent of Mitf function in mouse eye development. Our results suggest that the Mitf gene is the original member of the MitfTfe subfamily of bHLH-Zip proteins and that its developmental function is at least partially conserved between vertebrates and invertebrates. These findings further support the common origin of the vertebrate and invertebrate eyes.

Aberrant expression of miR-96 in prostate cancer has previously been reported. However, the role and mechanism of action of miR-96 in prostate cancer has not been determined. In this study, the diagnostic and prognostic properties of miR-96 expression levels were investigated by qRT-PCR in two well documented prostate cancer cohorts. The miR-96 expression was found to be significantly higher in prostate cancer patients and correlate with WHO grade, and decreased overall survival time; patients with low levels of miR-96 lived 1.5 years longer than patients with high miR-96 levels. The therapeutic potential was further investigated in vitro, showing that ectopic levels of miR-96 enhances growth and cellular proliferation in prostate cancer cells, implying that miR-96 has oncogenic properties in this setting. We demonstrate that miR-96 expression decreases the transcript and protein levels of FOXO1 by binding to one of two predicted binding sites in the FOXO1 3'UTR sequence. Blocking this binding site completely inhibited the growth enhancement conveyed by miR-96. This finding was corroborated in a large external prostate cancer patient cohort where miR-96 expression inversely correlated to FOXO1 expression. Taken together these findings indicate that miR-96 plays a key role in prostate cancer cellular proliferation and can enhance prostate cancer progression. This knowledge might be utilized for the development of novel therapeutic tools for prostate cancer.