Bone marrow mesenchymal stem cell-derived exosomal miR-206 inhibits osteosarcoma progression by targeting TRA2B

Cancer Lett. 2020 Oct 10:490:54-65. doi: 10.1016/j.canlet.2020.07.008. Epub 2020 Jul 16.

Abstract

Osteosarcoma is the most common primary malignant bone tumor in young people. Recently, extracellular vesicles, especially exosomes, have been reported to play an increasingly important role in the development of many types of tumors. In this research, we found that overexpression of transformer 2β (TRA2B) was associated with tumor progression in osteosarcoma, and TRA2B was the target gene of miR-206, which was downregulated in osteosarcoma tissues. Furthermore, we observed that bone marrow mesenchymal stem cell (BMSC)-derived exosomes could carry and transport miR-206 to osteosarcoma cells. Both in vitro and in vivo results showed that BMSC-derived exosomal miR-206 could inhibit the proliferation, migration and invasion of osteosarcoma cells and induce their apoptosis. Taken together, our study demonstrates that BMSC-derived exosomal miR-206 can be transferred into osteosarcoma cells and inhibit tumor progression by targeting TRA2B, which provides new insight into the molecular mechanism of osteosarcoma and highlights the potential of miR-206 and TRA2B as new therapeutic targets.

Keywords: Bone tumor; Extracellular vehicle; MicroRNA; Proliferation; Pulmonary metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Neoplasms / pathology*
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Disease Progression
  • Exosomes / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic / physiology
  • Humans
  • Mesenchymal Stem Cells / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / metabolism*
  • Nerve Tissue Proteins / metabolism*
  • Osteosarcoma / pathology*
  • Serine-Arginine Splicing Factors / metabolism*
  • Xenograft Model Antitumor Assays

Substances

  • MIRN206 microRNA, human
  • MicroRNAs
  • Nerve Tissue Proteins
  • TRA2B protein, human
  • Serine-Arginine Splicing Factors