Abstract 2527: The role of miR-601 in prostate cancer progression

Abstract

Abstract Prostate cancer (PCa) is the second most common cancer among men worldwide. In order to advance treatment options for these men, it is crucial to understand the molecular underpinnings behind this cancer. Previously, our group identified miR-601 as a biomarker of significance in PCa. Few studies to date have functionally validated molecular biomarkers and currently little is known about the function of miR-601 in PCa. Based on our previous publication, we hypothesized that miR-601 plays a role in PCa progression and radiation response. To test this hypothesis, miR-601 was over-expressed and knocked down in DU145 and PC3 cell lines and assays were performed evaluating cell proliferation, colony formation, apoptosis, and cell cycle progression. Additionally, to provide more information regarding miR-601-associated pathways, we identified putative gene targets of miR-601 using in silico prediction programs, microrna.org and TargetScan.org and evaluated top gene targets in vitro. To date, our data suggest that miR-601 may be playing a role as a tumor suppressor. Over-expression of miR-601 in cell lines resulted in a significant reduction in cell viability. This was confirmed both by MTS as well as colony formation assays. We looked into the mechanism behind the reduction in cell viability by testing the effect of miR-601 on apoptosis and cell cycle progression. We found that cells over-expressing miR-601 had slightly higher levels of apoptosis, however miR-601 did not induce a substantial effect on cell cycle progression. Additionally, we found that miR-601 enhances radiosensitization in DU145 and PC-3 cell lines. Similar results have been observed in breast cancer 1 as well as in a large miRNA screen performed in the LNCaP cell line2. Two putative gene targets of miR-601 were identified and investigated in vitro, SIRT1, a histone deacetylase known to be both an oncogene and tumor suppressor, and BCL2L2, an anti-apoptotic gene known to be an oncogene. SIRT1 and BCL2L2 had strong scores on both online prediction programs as likely targets of miR-601. Our in vitro results confirmed this. We saw reduced mRNA and protein expression of these targets in cells over-expressing miR-601. Our data thus far suggest that miR-601 is acting as a tumor suppressor in PCa. Targeted therapies for miR-601 and/or its targets may be promising in the treatment of PCa, however additional work is needed to validate this. Future work will focus on the role of miR-601 in cell migration and invasion as well on identifying the direct molecular mechanism(s) by which miR-601 is reducing cell viability and conveying radiation sensitivity. Funding: R01CA108633 (To AC), 1RC2CA148190 (To AC) U10CA180850-01 (To AC), 1R01CA169368 (To AC) from the NCI, Brain Tumor Funders Collaborative Grant (To AC), OSUCCC Award (To AC). 1. Hu JY et al. (2016) Biomedicine and Pharmacotherapy. 79: 247-53 2. Hatano K. et al. (2015) Nucleic Acids Research. 43: 4075-86 Citation Format: Jessica L. Fleming, Erica H. Bell, Kathryn Andrews, Arnab Chakravarti. The role of miR-601 in prostate cancer progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2527. doi:10.1158/1538-7445.AM2017-2527