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Hypoxic breast cancer cell-derived exosomal miR-143-3p targets RICTOR to regulate M2 macrophage polarization, thereby

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|May 30, 2025
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Summary

Hypoxia in breast cancer downregulates exosomal miR-143-3p, promoting M2 macrophage polarization and enhancing cancer cell invasion. This suggests miR-143-3p as a potential therapeutic target for breast cancer.

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Breast cancerCell migrationInvasionMacrophageMiR-143-3p

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Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Hypoxia is a key factor in tumor microenvironments, influencing cancer progression.
  • Exosomes mediate intercellular communication, transporting microRNAs (miRNAs) that regulate cancer metastasis.
  • Breast cancer progression is linked to macrophage polarization and epithelial-mesenchymal transition (EMT).

Purpose of the Study:

  • To investigate the role of hypoxic breast cancer cell-derived exosomal miR-143-3p in cancer progression.
  • To determine the mechanism by which hypoxia affects exosomal miR-143-3p and its impact on M2 macrophage polarization and breast cancer cell invasiveness.

Main Methods:

  • Real-time PCR to quantify miR-143-3p expression in exosomes.
  • Co-culturing breast cancer cells with M0 macrophages exposed to hypoxia-derived exosomes.
  • Transwell assays to assess breast cancer cell invasiveness.
  • Western blot to analyze M2 macrophage markers and EMT indicators.
  • Bioinformatics and dual luciferase reporter assay to confirm miR-143-3p and RICTOR interaction.

Main Results:

  • Exosomal miR-143-3p was downregulated under hypoxic conditions in breast cancer cells.
  • Hypoxic exosomes promoted M2 macrophage polarization (increased CD206, Arg-1, CD163 mRNA levels).
  • Exosome-mediated M2 polarization enhanced breast cancer cell migration and invasion.
  • miR-143-3p directly targets RICTOR, suppressing M2 polarization.

Conclusions:

  • Hypoxia downregulates exosomal miR-143-3p in breast cancer cells, leading to increased RICTOR expression in macrophages.
  • This process promotes M2 macrophage polarization and enhances breast cancer cell invasiveness.
  • Exosomal miR-143-3p is a potential therapeutic target for breast cancer treatment.