Exosomes derived from microRNA-101-3p-overexpressing human bone marrow mesenchymal stem cells suppress oral cancer cell proliferation, invasion, and migration

Mol Cell Biochem. 2019 Aug;458(1-2):11-26. doi: 10.1007/s11010-019-03526-7. Epub 2019 Jun 4.

Abstract

Dysregulation of microRNAs (miRNAs) has been found to disrupt the progression of oral cancer. However, which miRNAs are most effective against oral cancer and how these miRNAs should be delivered are major unanswered problems. We aimed at investigating if human bone marrow mesenchymal stem cells (hBMSCs)-derived exosomes affect oral cancer development, and the potential regulatory mechanism associated with COL10A1 and miR-101-3p. COL10A1 was upregulated, while miR-101-3p was downregulated in oral cancer, and miR-101-3p targeted COL10A1 as verified by dual-luciferase reporter gene assay. Meanwhile, exosomes derived from hBMSCs were isolated and then co-cultured with oral cancer cells to identify the role of exosomes, and the results suggested that hBMSCs-derived exosomes overexpressing miR-101-3p inhibited oral cancer progression. Furthermore, tumorigenicity assay in nude mice further confirmed the inhibitory effects of hBMSCs-derived exosomes, loaded with miR-101-3p, on oral cancer, which provides a new theoretical basis in the treatment of oral cancer.

Keywords: Collagen type X alpha 1 chain; Exosomes; Human bone marrow mesenchymal stem cells; MicroRNA-101-3p; Oral cancer.

MeSH terms

  • Aged
  • Animals
  • Bone Marrow Cells / metabolism*
  • Cell Movement*
  • Cell Proliferation*
  • Exosomes / metabolism
  • Exosomes / transplantation*
  • Female
  • HEK293 Cells
  • Humans
  • Male
  • Mesenchymal Stem Cells / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / biosynthesis*
  • Middle Aged
  • Mouth Neoplasms / metabolism
  • Mouth Neoplasms / pathology
  • Mouth Neoplasms / therapy*
  • Neoplasm Invasiveness
  • Xenograft Model Antitumor Assays

Substances

  • MIRN101 microRNA, human
  • MicroRNAs