Abstract 471: High expression of miR-182 promotes prostate cancer aggressiveness in African-Americans compared to Caucasians

Abstract

Abstract Background: African-Americans (AfA) have higher risk for developing prostate cancer and when diagnosed, the cancer is more aggressive with worse survival compared to Caucasians (CA). To clarify the mechanisms involved in this disparity, we analyzed the role of miR-182 in AfA and CA prostate cancer tissues and cells. Materials and Methods: We analyzed miR-182 expression in AfA and CA prostate cancer tissue samples by Real Time PCR. We selected two cell lines, DU-145 (CA) and MDA-PCa-2b (AfA), which express different levels of miR-182, to mimic the tissue samples and help identify the mechanisms related to racial disparity. We generated lentivirus stable miR-182 knockdown cells lines and performed cell viability assays using a CellTiter-Glo luminescent assay. For cell cycle analysis, cells were stained with PI/RNase staining buffer and analyzed for DNA content by BD FACSVerse. Cancer pathway-focused gene expression profiling was done using a human RT2 Profiler Cancer Pathway Finder and Oncogenes and Tumor Suppressor Genes PCR Array. Results: We found miR-182 expression to be higher in AfA prostate cancer tissues compared to CA patients with localized disease. Also, expression of miR-182 in AfA cell line, MDA-PCa-2b, was significantly higher compared to CA cell line, DU-145. To determine the role of miR-182 in the differences between AfA and CA, miR-182 was knocked down in MDA-PCa-2b and DU- 145 cells. miR-182 knockdown in MDA-PCa-2b cells effectively inhibited cell migration, invasion and colony formation compared to control cells, while there was no difference in DU-145 cells. Knockdown of miR-182 caused a decrease in MDA-PCa-2b cell viability compared with negative control. In addition, the cell cycle profile showed an increase in the G1 phase of MDA-PCa-2b cells (control 7.3% compared to miR-182 knockdown cells 18.6%), whereas no change was observed in DU-145 cells. Similar to these results, wound healing was significantly slower in the miR-182 knockdown MDA-PCa-2b cells compared to controls. PCR array analysis was performed to determine the molecular effects of miR-182 knockdown in MDA-PCa-2b and DU-145 cells. We found from our PCR array data some potential targets genes regulated by miR-182. Conclusion: We conclude that high levels of miR-182 is associated with prostate cancer aggressiveness in African-Americans. Citation Format: Marisa Shiina, Yutaka Hashimoto, Guoren Deng, Varahram Shahryari, Majid Shahana, Soichiro Yamamura, Priyanka Kulkarni, Pritha Dasgupta, Divya Bhagirath, Sharanjot Sharan, Yuichiro Tanaka, Rajvir Dahiya. High expression of miR-182 promotes prostate cancer aggressiveness in African-Americans compared to Caucasians [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 471.