Exosomal miR-1304-3p promotes breast cancer progression in African Americans by activating cancer-associated adipocytes

Dan Zhao, Kerui Wu, Sambad Sharma, Fei Xing, Shih-Ying Wu, Abhishek Tyagi, Ravindra Deshpande, Ravi Singh, Martin Wabitsch, Yin-Yuan Mo and Kounosuke Watabe ()
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Dan Zhao: Wake Forest University School of Medicine
Kerui Wu: Wake Forest University School of Medicine
Sambad Sharma: Wake Forest University School of Medicine
Fei Xing: Wake Forest University School of Medicine
Shih-Ying Wu: Wake Forest University School of Medicine
Abhishek Tyagi: Wake Forest University School of Medicine
Ravindra Deshpande: Wake Forest University School of Medicine
Ravi Singh: Wake Forest University School of Medicine
Martin Wabitsch: Ulm University Medical Center
Yin-Yuan Mo: University of Mississippi Medical Center
Kounosuke Watabe: Wake Forest University School of Medicine

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: Abstract Breast cancer displays disparities in mortality between African Americans and Caucasian Americans. However, the exact molecular mechanisms remain elusive. Here, we identify miR-1304-3p as the most upregulated microRNA in African American patients. Importantly, its expression significantly correlates with poor progression-free survival in African American patients. Ectopic expression of miR-1304 promotes tumor progression in vivo. Exosomal miR-1304-3p activates cancer-associated adipocytes that release lipids and enhance cancer cell growth. Moreover, we identify the anti-adipogenic gene GATA2 as the target of miR-1304-3p. Notably, a single nucleotide polymorphism (SNP) located in the miR-1304 stem-loop region shows a significant difference in frequencies of the G allele between African and Caucasian American groups, which promotes the maturation of miR-1304-3p. Therefore, our results reveal a mechanism of the disparity in breast cancer progression and suggest a potential utility of miR-1304-3p and the associated SNP as biomarkers for predicting the outcome of African American patients.

Date: 2022
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DOI: 10.1038/s41467-022-35305-2

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