Abstract In South Carolina, mortality differences between African American (AA) and non-Hispanic white (NHW) women breast cancer patients are amongst the highest in the country. Evidence suggests that the observed racial disparity exists independent of socioeconomic and standard of care issues, suggesting a potential biological factor may be involved. The loss of Caveolin-1 (Cav1) in the tumor stromal compartment has emerged as a novel biomarker for predicting poor clinical outcome in all of the most common subtypes of breast cancer, however the mechanism of Cav1 loss is unknown. We identified miR-510 as a novel oncomir and propose that its elevated expression in breast tumors results in stromal Cav1 loss and a subsequent worse outcome. In this study we used luciferase, western blot and quantitative PCR analysis to study Caveolin-1 as a direct target of miR-510. We used a co-culture system to assess crosstalk between epithelial and stromal compartments in vitro and a mouse model to assess this in vivo. Our research shows that Cav1 is a direct target of miR-510 and that overexpression of miR-510 leads to downregulation of Cav1 protein expression, specifically in the stromal compartment. This may be racially significant as our studies also show that miR-510 levels are elevated and Cav1 levels are reduced in AA breast cancer patients compared to their NHW counterparts. Data from our in vivo studies shows that cancer-associated fibroblasts (CAFs) isolated from miR-510 expressing epithelial derived tumors lead to more aggressive tumor growth when co-injected with breast tumor epithelial cells when compared to scrambled control CAF co-injections and breast tumor epithelial cells alone. Our results suggest that elevated miR-510 expression in breast epithelial cells leads to stromal Cav1 loss and is a mechanism driving racial disparity in breast cancer. Citation Format: David P. Turner, Brooke King, Qi Guo, Bobbie Blake, Lourdes M. Nogueira, amanda c. larue, judith d. salley, marvella e. ford, ashley evans-knowell, Victoria J. Findlay. MicroRNA mediated megative regulation of caveolin 1 as a biological mechanism driving breast cancer disparities. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr C32.