Abstract 1775: Differential expression of exosomes-associated onco-microRNAs in African Americans with prostate cancer

Abstract

Abstract Background: The mortality rate of prostate cancer (PCa) is two times higher in African American (AA) than Caucasian American (CA) men. The molecular mechanisms underlying these health disparities among AA men have yet to be fully elucidated. Our study aimed to evaluate the role of exosomes-associated onco-microRNAs (miRs) as biological determinant for the racial disparity of PCa patients. Methods: Exosomes were isolated from the conditioned medium of MDA-PCa-2b (AA-origin), PC-3 (CA origin), C4-2B and RWPE-1 (non-tumorigenic) cell lines to study the endogenous expression of a number of onco-miRs and their anticipated target genes using Real-Time PCR and Western blot analyses. The potential candidates were validated in exosomes procured from plasma of human AA PCa patients and their counterparts. Onco-miRs target genes such as Lats-2, PDCD4, and SMEK1 were validated on cellular and exosomes derived from cells and human specimens. Onco-miRs and their targets were correlated with age and Gleason score of the disease. Results: Not only onco-miR-125b, miR-155, and miR-3613 were upregulated in PCa versus normal RWPE1 cells but also in AA versus CA PCa cells. Onc-miR-3613 and miR-3680 were 3-4 times upregulated in cells and in C4-2B-derived exosomes compared to RWPE-1-derived vesicles. Also, these miRs were upregulated (∼2.5 fold) in MDA-PCa-2b versus PC-3 cells. The expression of tumor suppressor genes, such as Lats2, PDCD4, and SMEK1, were downregulated in PCa cells compared to normal cells. Differential expression of PCa exosomes-associated onco-miRs was also demonstrated in AA PCa patients compared to CA PCa and their age-matched normal subjects. A positive correlation was found between onco-miR-125b and high Gleason score (r = 0.763, p<0.01). Conclusion: Our findings underline the role of exosomes-associated onco-miRs in health disparity of PCa. The differential expression of onco-miRs and their tumor suppressor genes in AA men projects their potential role as prognostic markers and/or future therapeutic targets in the context of racial disparity. Citation Format: Ahmed A. Moustafa, Andrew B. Sholl, Koji Tsumagari, Mohamed Hassan, Emad Kandil, Asim B. Abdel-Mageed, Zakaria Y. Abd Elmageed. Differential expression of exosomes-associated onco-microRNAs in African Americans with prostate cancer. [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 1775.