High expression of miR-17-5p in tumor epithelium is a predictor for poor prognosis for prostate cancer patients.

MicroRNAs (miRs) are small non-coding RNA molecules, which are involved in the development of various malignancies, including prostate cancer (PCa). miR-17-5p is considered the most prominent member of the miR-17-92 cluster, with an essential regulatory function of fundamental cellular processes. In many malignancies, up-regulation of miR-17-5p is associated with worse outcome. In PCa, miR-17-5p has been reported to increase cell proliferation and the risk of metastasis. In this study, prostatectomy specimens from 535 patients were collected. Tissue microarrays were constructed and in situ hybridization was performed, followed by scoring of miR-17-5p expression on different tumor compartments. High expression of miR-17-5p in tumor epithelium was associated with biochemical failure (BF, p < 0.001) and clinical failure (CF, p = 0.019). In multivariate analyses, high miR-17-5p expression in tumor epithelial cells was an independent negative prognostic factor for BF (HR 1.87, 95% CI 1.32-2.67, p < 0.001). In vitro analyses confirmed association between overexpression of miR-17-5p and proliferation, migration and invasion in prostate cancer cell lines (PC3 and DU145). In conclusion, our study suggests that a high cancer cell expression of miR-17-5p was an independent negative prognostic factor in PCa.

Expression and regulation of the estrogen receptors in PC-3 human prostate cancer cells.

The aim of this study was to identify the expression, cellular localization and regulation of classic estrogen receptors ERα and ERß, ER-α36 isoform and GPER in the androgen-independent prostate cancer cell line PC-3. In addition, we evaluated the relative contribution of these receptors to the activation of the ERK1/2 (extracellular signal-regulated protein kinases) signaling pathway. These four estrogen receptors were detected by Western blot assays and were shown by immunofluorescence assays to localize preferentially in extranuclear regions of PC-3 cells. In addition, treatment with 17ß-estradiol (E2) (1 µM) for 24 h led to down-regulation of the classic estrogen receptors, whereas E2 at physiological concentration (0.1 nM) for 24h tended to increase the levels of ERα and ERß. Furthermore, the ERα-selective agonist PPT selectively increased the expression of ERß and the ERß-selective agonist DPN increased ERα levels. None of these treatments affected expression of the ER-α36 isoform. The unusual cytoplasmic localization of the classic estrogen receptors in these cells differs from the nuclear localization in the majority of estrogen target cells and suggests that rapid signaling pathways may be preferentially activated. In fact, treatment with selective agonists of ERα, ERß and GPER induced ERK1/2 phosphorylation that was blocked by the respective antagonists. On the other hand, activation of ERK1/2 induced by E2 may involve additional mechanisms because it was not blocked by the three antagonists. Taken together, the results indicate that there is a crosstalk between ERα and ERß to regulate the expression of each other, and suggest the involvement of other receptors, such as ER-α36, in the rapid ERK1/2 activation by E2. The identification of new isoforms of ERs, regulation of the receptors and signaling pathways is important to develop new therapeutic strategies for the castration-resistant prostate cancer.