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hUC-MSCs secreted exosomes inhibit the glioma cell progression through PTENP1/miR-10a-5p/PTEN pathway

Eur Rev Med Pharmacol Sci. 2019 Nov;23(22):10013-10023. doi: 10.26355/eurrev_201911_19568.

Abstract

Objective: The mesenchymal stem cells (MSCs) have been widely studied for their anti-tumor property, due to the characteristic of homing towards tumor sites and immunosuppression. Nevertheless, the underlying molecular mechanisms that link MSCs to the targeted tumor cells, such as glioma, are not clear.

Materials and methods: Here, we examined the inhibitory properties and new molecular mechanisms of the human umbilical cord (hUC-MSCs) derived exosomes on the human glioma U87 cells using a co-culture system in vitro. The cell counting kit-8 (CCK-8) assay was performed to measure the anti-tumor activity of hUC-MSCs derived exosomes. The cell apoptosis was assessed by flow cytometry and the immunoblotting assay was applied in order to assess the associated proteins level. The data revealed that hUC-MSCs derived exosomes could repress cell proliferation and induce cell apoptosis.

Results: Mechanistically, we identified that lncRNA PTENP1 could be packaged into exosome from hUC-MSCs, transferred to U87 cells, and then stabilized PTEN by binding miR-10a-5p competitively.

Conclusions: Therefore, our data suggested that the exosomes from hUC-MSCs possess a higher anti-tumor capacity, at least partially, via regulating miR-10a-5p/PTEN signaling, which thereby may represent a possible target for early diagnosis and treatment of glioma clinically.

MeSH terms

  • Apoptosis
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / metabolism
  • Cell Differentiation
  • Cell Line, Tumor
  • Cell Proliferation
  • Coculture Techniques
  • Disease Progression
  • Exosomes / genetics*
  • Exosomes / metabolism
  • Female
  • Glioma / genetics*
  • Glioma / metabolism
  • Humans
  • Mesenchymal Stem Cells / chemistry
  • Mesenchymal Stem Cells / cytology
  • MicroRNAs / genetics*
  • PTEN Phosphohydrolase / genetics*
  • Pregnancy
  • RNA, Long Noncoding / genetics*
  • Signal Transduction
  • Umbilical Cord / chemistry
  • Umbilical Cord / cytology*

Substances

  • MIRN10 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • PTEN Phosphohydrolase
  • PTEN protein, human