Exosomal miRNA-21 from Toxoplasma gondii-infected microglial cells induces the growth of U87 glioma cells by inhibiting tumor suppressor genes

Sci Rep. 2022 Sep 30;12(1):16450. doi: 10.1038/s41598-022-20281-w.

Abstract

Toxoplasma gondii is an intracellular protozoan parasite that can modulate the microenvironment of infected hosts and is known to be associated with the incidence of brain tumor growth. In this study, we suggested that the exosomal microRNA-21 derived from Toxoplasma infection would contribute to the growth of brain tumors. Exosomes of BV2 microglial cells infected with Toxoplasma were characterized and confirmed internalization to U87 glioma cells. Exosomal miRNA expression profiles were analyzed using microRNA array and miR-21A-5p associated with Toxoplasma and tumor sorted. We also examined the mRNA level of tumor-associated genes in U87 glioma cells by changing the level of miR-21 within exosomes and the effects of exosomes on the proliferation of human U87 glioma cells. Expression of miRNA-21 was increased and anti-tumorigenic genes (FoxO1, PTEN, and PDCD4) were decreased in exosomes within T. gondii-infected U87 glioma cells. Toxoplasma-infected BV2-derived exosomes induced proliferation of U87 glioma cells. The exosomes induced the growth of U87 cells in a mouse tumor model. We suggest that the increased exosomal miR-21 from Toxoplasma-infected BV2 microglial cells may play an important role as a cell growth promotor of U87 glioma cells through a down-regulation of anti-tumorigenic genes.

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins / metabolism
  • Brain Neoplasms* / pathology
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Exosomes* / metabolism
  • Genes, Tumor Suppressor
  • Glioma* / pathology
  • Humans
  • Mice
  • MicroRNAs* / metabolism
  • Microglia / metabolism
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / metabolism
  • Toxoplasma* / genetics
  • Toxoplasma* / metabolism
  • Tumor Microenvironment

Substances

  • Apoptosis Regulatory Proteins
  • MIRN21 microRNA, human
  • MicroRNAs
  • PDCD4 protein, human
  • RNA, Messenger
  • RNA-Binding Proteins