Exosomal miR-1910-3p promotes proliferation, metastasis, and autophagy of breast cancer cells by targeting MTMR3 and activating the NF-κB signaling pathway

Cancer Lett. 2020 Oct 1:489:87-99. doi: 10.1016/j.canlet.2020.05.038. Epub 2020 Jun 9.

Abstract

Exosomes are key mediators of intercellular communication and play a role in the pathogenesis and progression of cancer. Exosomes in circulating body fluids serve as molecular markers for cancer diagnosis. This study aimed to investigate the role of exosomal microRNA (miR)-1910-3p in breast cancer and determine its clinical diagnostic value. MiR-1910-3p promoted proliferation and migration of breast cancer cells in vitro and in vivo. In vitro, exosomes enriched in miR-1910-3p transferred miR-1910-3p to mammary epithelial cells and breast cancer cells, promoting proliferation and migration, inhibiting apoptosis, and inducing autophagy. In vivo, exosomes enriched in miR-1910-3p promoted the proliferation and migration of breast cancer cells. MiR-1910-3p downregulated myotubularin-related protein 3, activated the NF-κB and wnt/β-catenin signaling pathway, and promoted breast cancer progression. Serum miR-1910-3p in exosomes was an effective diagnostic marker that improved the sensitivity of breast cancer diagnosis when used in combination with the traditional tumor marker CA153. In conclusion, breast cancer cell-derived exosomes promoted the growth, metastasis, and autophagy of breast cancer cells by transferring miR-1910-3p. MiR-1910-3p in serum exosomes may serve as a novel molecular marker for breast cancer diagnosis.

Keywords: Breast cancer; Exosome; Metastasis; Proliferation; miR-1910-3p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy / physiology
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / genetics
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology*
  • Cell Proliferation / genetics
  • Exosomes / genetics
  • Exosomes / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic / physiology*
  • Heterografts
  • Humans
  • Mice
  • MicroRNAs / metabolism*
  • NF-kappa B / metabolism*
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Protein Tyrosine Phosphatases, Non-Receptor / metabolism*
  • Signal Transduction / physiology

Substances

  • Biomarkers, Tumor
  • MIRN1910-3p microRNA, human
  • MicroRNAs
  • NF-kappa B
  • MTMR3 protein, human
  • Protein Tyrosine Phosphatases, Non-Receptor