Abstract 4840: The role of miR-146a and novel Rhenium compounds on prostate cancer cell lines derived from African Americans and European American patients

Abstract

Abstract African American (AA) men have disproportionately high incidence and mortality rates of prostate cancer (PCa) compared to other ethnic groups in the United States. The identification of molecular factors that contribute to this disparity could improve diagnosis and may predict therapeutic efficacy. MicroRNA-146a (miR-146a) suppresses PCa transformation from androgen-dependent to -independent state, and suppresses a kinase coding gene which reduces cell proliferation, invasion and metastasis. It is anticipated that miR-146a and other miRNAs may one day become biomarkers for clinical diagnosis and prognosis of several types of cancer including PCa. Novel rhenium compounds have shown anti-cancer properties especially in PCa. Therefore, the purpose of this study was to determine the expression of miR-146a in PCa cell lines derived from AA and European American (EA) patients. We also investigated the anti-cancer properties of two novel organorhenium pentylcarbonate (RPC) compounds. Relative levels of miRNA expression was determined by qRT-PCR, miRNA plate assay and smart flare technology after isolating total RNA from the cells and the exosomes from the tumor microenvironment. Cytotoxicity studies of the RPC compounds were done by using MTT and Trypan Blue assay. Our data showed a several fold increase in the expression of miR-146a in PCa cells derived from AA patient in comparison to cells derived from EA patients and a benign cell line. The RPC compounds showed bioactivity in all the PCa lines. To date, we are unaware of any studies that compared the miR-146a expression in PCa cells derived from the two racial groups. Our study suggests that miR-146a is up-regulated in PCa cells derived from AA patient compared to EA patient, which could possibly contribute to the aggressiveness associated in AA patients. We also found that the novel organorhenium compounds are bioactive with anti-cancer properties. Our results warrant further studies which are being done by our laboratory for assessing the mechanistic role of miR-146a associated with the anti-cancer activity of rhenium compounds and the role of miR-146a to define the racial disparity in PCa patients. Acknowledgment: This research was supported by a grant from the Borroughs Wellcome Fund, NSF-LSAMP, NIH-MARC and a Disability Supplement grant from NIH. Citation Format: Monet Stevenson, Jameel Joyner, Khadija Dildar, Oladipo Adedeji, Krishnan Prabhakaran, Hirendra N. Banerjee, Santosh Mandal, Fazlul Sarkar. The role of miR-146a and novel Rhenium compounds on prostate cancer cell lines derived from African Americans and European American patients. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4840. doi:10.1158/1538-7445.AM2015-4840