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...

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Bibliographic Details
Published in:	Nature communications 2022-12, Vol.13 (1), p.7734-7734, Article 7734
Main Authors:	Zhao, Dan, Wu, Kerui, Sharma, Sambad, Xing, Fei, Wu, Shih-Ying, Tyagi, Abhishek, Deshpande, Ravindra, Singh, Ravi, Wabitsch, Martin, Mo, Yin-Yuan, Watabe, Kounosuke
Format:	Article
Language:	eng
Subjects:	Adipocytes Adipocytes - metabolism African Americans Biomarkers Black or African American - genetics Breast cancer Breast Neoplasms - ethnology Breast Neoplasms - genetics Breast Neoplasms - metabolism Breast Neoplasms - pathology Cell Proliferation Ectopic expression Exosomes - genetics Exosomes - metabolism Female Gene Expression Regulation, Neoplastic Gene polymorphism Humans Lipids MicroRNAs MicroRNAs - genetics MicroRNAs - metabolism Minority & ethnic groups miRNA Molecular modelling Mortality Nucleotides Polymorphism Race factors Ribonucleic acid RNA Single-nucleotide polymorphism Tumors White people
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Summary:	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.
ISSN:	2041-1723 2041-1723