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Tumor Cell-Derived Exosomal miR-191-5p Activates M2-Subtype Macrophages Through SOCS3 to Facilitate Breast Cancer

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Abstract

Differential activation of macrophages is associated with poor progression of breast cancer (BC). Many reports have elucidated the important involvement of exosomes produced by cancer cells in remodeling the macrophage activation phenotype to promote tumor expansion and invasion. However, the underlying mechanisms by which exosomes secreted by BC cells facilitate macrophage M2 polarization remain enigmatic and worth exploring. In this study, quantitative real-time PCR (RT-qPCR) was used to investigate miR-191-5p expression in BC tumor tissues and cells. Cell counting kit 8 (CCK-8), transwell, and flow cytometry were applied to assess the functional role of miR-191-5p in BC. Isolated nano-vesicles were identified using transmission electron microscopy and western blotting. We also observed that miR-191-5p was significantly elevated in BC clinical samples and that inhibition of miR-191-5p hindered the growth and metastasis of BC cells. Importantly, BC cells successfully accelerated macrophage M2-like polarization by directly transferring exosomes to macrophages, resulting in increased miR-191-5p levels in macrophages. Mechanistically, exosomal miR-191-5p directly inhibited the suppressors of cytokine signaling 3 (SOCS3) expression in macrophages and aggravated macrophage M2 polarization. Similarly, si-SOCS3 transfected macrophages boosted BC cell migration and invasion in a positive feedback manner. Overall, our results manifested a pro-growth and pro-metastatic role between the two cells by elucidating the crucial role of exosomal miR-191-5p in stimulating M2 macrophage polarization and mediating communication between BC cells and macrophages. These findings opened up new horizons for the development of BC therapeutic strategies.

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Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Authors and Affiliations

  1. Department of Breast Surgery, People’s Hospital of Ganzhou City, Ganzhou, 314000, Jiangxi, China

    Jun Ni, Xun Xi & Sujian Xiao

  2. Department of General Surgery, People’s Hospital of Ganzhou City, No.16, Meiguan Road, Ganzhou, 314000, Jiangxi, China

    Xigang Xiao

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  1. Jun Ni
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Contributions

JN designed the study and draft the manuscript. XX acquired and processed the data. SX partly contributed to the experiment. XX wrote, reviewed, and revised the paper. All authors reviewed the results and approved the final version of the manuscript.

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Correspondence to Xigang Xiao.

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The authors declare that they have no conflicts of interest to report regarding the present study.

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All participants were provided with written informed consent at the time of recruitment. This study was approved by the Ethics Committee of People’s Hospital of Ganzhou City, and all experiments involving human tissue specimens comply with the Declaration of Helsinki.

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Ni, J., Xi, X., Xiao, S. et al. Tumor Cell-Derived Exosomal miR-191-5p Activates M2-Subtype Macrophages Through SOCS3 to Facilitate Breast Cancer. Mol Biotechnol 66, 1314–1325 (2024). https://doi.org/10.1007/s12033-023-01034-0

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