Abstract 1906: Inhibition of miR-186 and repression of aggressive prostate cancer phenotype using a metastatic cell model

Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LA MicroRNA (miR) dysregulation alters the expression of cancer related genes and contributes to disease states in many cancers. For example, ectopic miR-186 expression leads to enhanced cell proliferation and migration in pancreatic cancer. However, the role of miR-186 in prostate cancer (PCa) remains unclear. Previously, we observed significant upregulation of miR-186-5p in PCa patient serum (stage III/IV) compared to controls. Furthermore, miR-186 was significantly up-regulated in metastatic PCa (PC-3) compared to normal prostate epithelial cells (RWPE1). We hypothesized miR-186 inhibition will reduce aggressive PCa in vitro. Consequently, miR-186 was transiently and stably inhibited in PC-3 cells. Cell proliferation and colony formation were evaluated for 7 and 21 days via Trypan Blue exclusion and soft agar assays. Aberrant gene expression was evaluated in transfected cells to identify miR-186 targets. Candidate miR-186 targets were selected using published reports on ‘miR-186 and cancer’, availability of robust antibodies, and statistical filtering (false discovery ≥0.05 and ±1.2 fold change). Mir-186 inhibition in PC-3 cells significantly repressed proliferation and colony formation by 34-64%. Following miR-186 inhibition in PC-3 cells, 2,343 identified mRNA targets were differentially expressed compared to scramble controls (p < 0.05). The target list was reduced to 11 up-regulated candidates. Predicted miR-186 targets are undergoing validation via qRT-PCR, western blots, and luciferase reporter assays. In addition, other studies are in progress to evaluate the impact of miR-186 on cellular proliferation, migration and invasion. Such efforts may lead to the identification of novel biomarkers to improve detection and clinical management strategies for aggressive PCa. Citation Format: Dominique Z. Jones, M. Lee Schmidt, Katharine R. Hobbing, Geoffrey Clark, LaCreis R. Kidd. Inhibition of miR-186 and repression of aggressive prostate cancer phenotype using a metastatic cell model. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1906.