Exosomes derived from microRNA-512-5p-transfected bone mesenchymal stem cells inhibit glioblastoma progression by targeting JAG1

Aging (Albany NY). 2021 Mar 26;13(7):9911-9926. doi: 10.18632/aging.202747. Epub 2021 Mar 26.

Abstract

In this study, we demonstrate that bone mesenchymal stem cell (BMSC)-derived exosomes alter tumor phenotypes by delivering miR-512-5p. miR-512-5p was downregulated in glioblastoma tissues and cells, and Jagged 1 (JAG1) was the target gene of miR-512-5p. We clarified the expression patterns of miR-512-5p and JAG1 along with their interactions in glioblastoma. Additionally, we observed that BMSC-derived exosomes could contain and transport miR-512-5p to glioblastoma cells in vitro. BMSC-derived exosomal miR-512-5p inhibited glioblastoma cell proliferation and induced cell cycle arrest by suppressing JAG1 expression. In vivo assays validated the in vitro findings, with BMSC-exosomal miR-512-5p inhibiting glioblastoma growth and prolonging survival in mice. These results suggest that BMSC-derived exosomes transport miR-512-5p into glioblastoma and slow its progression by targeting JAG1. This study reveals a new molecular mechanism for glioblastoma treatment and validates miRNA packaging into exosomes for glioblastoma cell communication.

Keywords: bone mesenchymal stem cell (BMSC); exosomes; glioblastoma (GBM); jagged 1 (JAG1); miR-512-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Cell Cycle Checkpoints / physiology
  • Cell Proliferation / physiology
  • Disease Progression
  • Down-Regulation
  • Exosomes / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Glioblastoma / metabolism*
  • Glioblastoma / pathology
  • Humans
  • Jagged-1 Protein / metabolism*
  • Mesenchymal Stem Cells / metabolism*
  • Mice
  • Mice, Nude
  • MicroRNAs / metabolism*
  • Middle Aged

Substances

  • JAG1 protein, human
  • Jagged-1 Protein
  • MIRN512 microRNA, human
  • MicroRNAs