Altered expression of exosomal microRNAs in Toxoplasma gondii-infected BV2 microglial cells : Its role in regeneration of glioblastoma cells

Abstract

ABSTRACT

Altered expression of exosomal microRNAs in Toxoplasma gondii-infected BV2 microglial cells : Its role in regeneration of glioblastoma cells

Hyemi Song Department of Molecular Medicine and Biopharmaceutical Science, The Graduate School of Convergence Science and Technology, Seoul National University

Toxoplasma gondii (T. gondii) is an intracellular protozoan parasite that modulates the environment of the infected host. Exosomal microRNAs derived from various protozoan-infected host cells are known to be a regulator for survival of parasites through inhibition of microbicidal functions of the infected host cells. The favorable environment manipulated by Toxoplasma resembles tumor microenvironment and may help to induce the incidences of brain tumors. However, the possible mechanisms involved in Toxoplasma infection inducing brain tumors are not well understood. In this study, in order to investigate the possible role of Toxoplasma infection in brain tumor development, the author isolated and characterized the exosomes from murine microglial cells (BV2 cells) infected with RH or ME49 strain of T. gondii. The author analyzed exosomal miRNAs expression profiles by microRNA array in the BV2 cells and validated them by quantitative reverse-transcription PCR (qRT-PCR) in part. Fourteen miRNAs known to be related to tumor or host immunity were significantly altered in both RH and ME49 strain Toxoplasma-infected BV2 cells. The author used various web tools such as functional disease ontology analysis, i.e., FunDO, for the purpose to find out related diseases involved with the targeted genes of the significantly regulated miRNAs. As a result, altered miRNAs by Toxoplasma infection showed the positive correlations with tumor progression and the brain tumor was mainly related to the predicted genes of up-regulated miRNAs (P < 0.05). Furthermore, the author confirmed that Toxoplasma-infected BV2 exosomes could be internalized by host cells and induced the regeneration of U87 glioblastoma cells in vitro. These results supported the close relationship between Toxoplasma and glioblastoma regeneration. In conclusion, the author confirmed altered expression of exosomal miRNAs in Toxoplasma-infected BV2 microglial cells and certainly suggested that Toxoplasma-infected microglia cell-derived exosomes play an important role as a regulator for the regeneration of glioblastoma cells.

Keywords: Toxoplasma gondii, Microglial cell, Exosome, microRNA, glioblastoma Student Number: 2013-22729