Abstract 1091: miR-125 family of miRNAs mediates prostate cancer cell proliferation and migration

Abstract

Abstract Background: Prostate cancer is the second most common malignancy in American men and causes ∼27540 deaths per annum. microRNAs (miRNAs) are a class of short non-coding RNAs that regulate the expression of protein-coding genes via either mRNA degradation or translational repression. These small molecules are known to be aberrantly expressed in prostate cancer (PCa) and possess both tumor suppressive and oncogenic properties. miR-125 is a highly conserved miRNA family comprised of three homolog members hsa-miR-125a, hsa-miR-125b-1, and hsa-miR-125b-2. Members of this family have been attributed both disease suppressing and promoting functions in certain contexts however their role in PCa has yet to be fully elucidated. Methods: miRNA expression was evaluated in a publicly available dataset (GSE21032) comprised of 28 normal, 98 primary PCa and 13 metastasis samples. miR-125 expression was assessed in a panel of 8 prostate cell lines comprising PrEC prostate epithelial cells, RWPE-1, BPH1, DU145, LNCaP, C4-2B, PC3, and PC3-2M cell lines using the Qiagen miScript system. MirWalk was used to identify predicted targets of the miRNAs. miR-125 expression was transiently inhibited in LNCaP, C4-2B, PC3, and PC3-2M cell lines using miScript miRNA inhibitors and miRNA and target mRNA expression, cell proliferation and migration were measured post-transfection. Results: Analysis of human data revealed miR-125a-3p was significantly up-regulated in metastasis samples compared to both primary PCa and normal tissues (log fold change (FC) 1.743, p-value 9.01E-08 logFC = 1.536 p-value = 8.80E-08 respectively). Next, we validated miR-125 family member expression in prostate cancer cell lines compared to PrEC and RWPE-1 prostate epithelial cells. Most notably, we observed that miR-125b-2 expression was significantly higher in all prostate cancer cell lines. Inhibition of miR-125b-2, significantly reduced the proliferation of the LNCaP, C4-2B, and PC3-2M cell lines. Moreover, inhibition of this miRNA significantly impaired prostate cancer cell migration by 43.8% (p-value = 0.003). Using MirWalk, we examined potential targets for regulation by miR-125b-2 and identified the potent tumor suppressor Quaking family as top hit. Our results show that inhibition of miR-125b-2 significantly enhanced the expression of Quaking family members (1.79 fold). Conclusions: Our results demonstrate that the miR-125 family of miRNAs plays a role in regulating prostate cancer cell proliferation and migration, potentially by mitigating Quaking activity. Citation Format: Sinead T. Aherne, Fiona O’Neill, Stephen F. Madden, Martin Clynes, Conor C. Lynch. miR-125 family of miRNAs mediates prostate cancer cell proliferation and migration. [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 1091.