Endocrine Abstracts

Prostate cancer (PC), the most commonly diagnosed malignancy among men, is a complex and heterogeneous disease that is highly influenced by the endocrine environment, which makes difficult the identification of novel therapeutic biomarkers to treat this pathology. Somatostatin (SST) is a pleiotropic neuropeptide that exerts its multiple biological functions, including tumor cell regulation, through a family of receptors (named sst1-5). Particularly, in this study we have found that sst1 is overexpressed in human PC samples compared with normal prostate (NP); however, the functional relevance of these alterations in PC is still unknown. Therefore, we aim to determine the potential functional role and mechanism of action of sst1 in human PC cells (using 22Rv1 and C42B cell lines). Functional parameters (i.e. proliferation and/or signaling pathways) were analyzed in response to treatments with two sst1-agonists or by silencing sst1 expression (using small interfering RNA). Moreover, we analyzed potential microRNAs (miRNAs) that could regulate sst1 expression in PC (using in silico approaches) and then, some selected miRNAs were used to perform functional assays. Our results showed that treatment with sst1-agonist decreased, while silencing of sst1 expression increased, cell proliferation in 22Rv1 cells. The effects of sst1-agonist in these PC cells were probably mediated through the regulation of AKT and PTEN but not ERK or calcium mobilization. In silico analyses revealed four putative miRNAs (miR-24/27/383/488) that could interact with sst1 at the 3′UTR. Interestingly, these miRNAs were negatively correlated with sst1 in 414 tumors (using The Cancer Genome Atlas (TCGA) data portal). Moreover, overexpression of miR-24 decreased sst1 expression, cell proliferation and migration, but increased cell death, in 22Rv1 and/or C42B cells. Finally, an inverse correlation between sst1 and miR-24 expression was found using the MSKCC dataset which include the combined analysis of 29 NP, 131 primary PC and 19 metastatic PC samples (i.e. expression of miR-24 gradually decreased, while sst1 expression increased, in these samples). In conclusion, our results indicate that sst1 is over-expressed in PC, where it can exert a relevant pathophysiological role by enhancing cell proliferation through AKT and PTEN signaling pathways. The observation that miR-24 can regulate sst1 expression and aggressiveness features in PC cells supports the idea that the combination of sst1 and miR-24 expression might be used as a novel tool to explore therapeutic targets in PC.