Exosomal miR-1304-3p promotes breast cancer progression in African Americans by activating cancer-associated adipocytes
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Dec 14, 2022
- Source ID
- 10.1038/s41467-022-35305-2
Entities
People
- Abhishek Tyagi
- Dan Zhao
- Fei Xing
- Kerui Wu
- Kounosuke Watabe
- Martin Wabitsch
- Ravi N Singh
- Ravindra Deshpande
- Sambad Sharma
- Shih-ying Wu
- Yin-Yuan Mo
Organizations
- National Cancer Institute
- United States Department of Defense