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

Author

Listed:
  • Dan Zhao

    (Wake Forest University School of Medicine
    University of Texas Southwestern Medical Center)

  • 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)

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.

Suggested Citation

  • Dan Zhao & Kerui Wu & Sambad Sharma & Fei Xing & Shih-Ying Wu & Abhishek Tyagi & Ravindra Deshpande & Ravi Singh & Martin Wabitsch & Yin-Yuan Mo & Kounosuke Watabe, 2022. "Exosomal miR-1304-3p promotes breast cancer progression in African Americans by activating cancer-associated adipocytes," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35305-2
    DOI: 10.1038/s41467-022-35305-2
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    References listed on IDEAS

    as
    1. Zhicheng Zeng & Yuling Li & Yangjian Pan & Xiaoliang Lan & Fuyao Song & Jingbo Sun & Kun Zhou & Xiaolong Liu & Xiaoli Ren & Feifei Wang & Jinlong Hu & Xiaohui Zhu & Wei Yang & Wenting Liao & Guoxin Li, 2018. "Cancer-derived exosomal miR-25-3p promotes pre-metastatic niche formation by inducing vascular permeability and angiogenesis," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    2. Kerui Wu & Jiamei Feng & Feng Lyu & Fei Xing & Sambad Sharma & Yin Liu & Shih-Ying Wu & Dan Zhao & Abhishek Tyagi & Ravindra Pramod Deshpande & Xinhong Pei & Marco Gabril Ruiz & Hiroyuki Takahashi & S, 2021. "Exosomal miR-19a and IBSP cooperate to induce osteolytic bone metastasis of estrogen receptor-positive breast cancer," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    3. Tian Fang & Hongwei Lv & Guishuai Lv & Ting Li & Changzheng Wang & Qin Han & Lexing Yu & Bo Su & Linna Guo & Shanna Huang & Dan Cao & Liang Tang & Shanhua Tang & Mengchao Wu & Wen Yang & Hongyang Wang, 2018. "Tumor-derived exosomal miR-1247-3p induces cancer-associated fibroblast activation to foster lung metastasis of liver cancer," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
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