MicroRNA-510 mediated negative regulation of Caveolin-1 in fibroblasts promotes aggressive tumor growth

Frontiers in Immunology

Immunology

Ashley Evans-Knowell¹  Arabia Satterwhite¹  Qi J. Guo²  Bobbie Blake²  Lourdes M. Nogueira²  Brooke King²  David P. Turner³  Victoria J. Findlay³  Bradley A. Krisanits⁴  Stanley Hoffman⁵  Gurbani Jolly⁶ 

[1] Department of Biological and Physical Sciences, South Carolina State University, Orangeburg, SC, United States;Department of Pathology & Laboratory Medicine, Medical University of South Carolina, Charleston, SC, United States;Department of Pathology & Laboratory Medicine, Medical University of South Carolina, Charleston, SC, United States;Department of Surgery, Massey Cancer Center, Virginia Commonwealth University, Richmond, VA, United States;Department of Surgery, Massey Cancer Center, Virginia Commonwealth University, Richmond, VA, United States;Division of Rheumatology, Department of Medicine, Medical University of South Carolina, Charleston, SC, United States;School of Medicine, Virginia Commonwealth University, Richmond, VA, United States;

关键词: Caveolin-1;    microRNA;    breast cancer;    disparities;    stroma;   

DOI  :  10.3389/fimmu.2023.1116644

 received in 2022-12-05, accepted in 2023-09-05,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionIn the US, despite the recent decline in breast cancer deaths, a persistent mortality disparity exists between black and white women with breast cancer, with black women having a 41% higher death rate. Several studies are now reporting that racial disparities can exist independent of socioeconomic and standard of care issues, suggesting that biological factors may be involved. Caveolin-1 (Cav1) loss in the tumor stromal compartment is a novel clinical biomarker for predicting poor outcome in breast cancer including triple negative subtype, however the mechanism of Cav1 loss is unknown. We previously identified miR-510-5p as a novel oncomir and propose here that the high levels observed in patients is a novel mechanism leading to stromal Cav1 loss and worse outcomes.MethodsCav1 was identified as a direct target of miR-510-5p through luciferase, western blot and qPCR assays. Stromal cross talk between epithelial cells and fibroblasts was assessed in vitro using transwell co-culture assays and in vivo using xenograft assays.ResultsWe found that Cav1 is a direct target of miR-510-5p and that expression in fibroblasts results in an ‘activated’ phenotype. We propose that this could be important in the context of cancer disparities as we also observed increased levels of circulating miR-510-5p and reduced levels of stromal Cav1 in black women compared to white women with breast cancer. Finally, we observed a significant increase in tumor growth when tumor cells were co-injected with miR-510-5p expressing cancer associated fibroblasts in vivo.ConclusionWe propose that miR-510-5p mediated negative regulation of Cav1 in fibroblasts is a novel mechanism of aggressive tumor growth and may be a driver of breast cancer disparity.

【 授权许可】

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Copyright © 2023 King, Krisanits, Guo, Blake, Nogueira, Jolly, Satterwhite, Turner, Hoffman, Evans-Knowell and Findlay