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

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. The molecular mechanisms explaining racial disparity in breast cancer mortality are not completely elucidated. Here, the authors show that an African-associated SNP in American breast cancer patients, leads to higher levels of microRNA miR-1304-3p which promotes cancer by increasing lipids availability.

Automated summary

This study reveals that miR-1304-3p is highly upregulated in African American breast cancer patients and its expression is associated with poor progression-free survival. miR-1304 promotes tumor progression by activating cancer-associated adipocytes that release lipids and enhance cancer cell growth. The anti-adipogenic gene GATA2 is identified as the target of miR-1304-3p. Additionally, a single nucleotide polymorphism (SNP) in the miR-1304 stem-loop region shows a significant difference in frequency between African and Caucasian American groups, influencing the maturation of miR-1304-3p.