Microglia exosomes miR-7239-3p promoting Glioma progression by regulating the Circadian genes

Background Glioma associated microglial cells (GAMs), as an important component of the tumor microenvironment (TME) play an important role in glioma progression. Materials & Methods Mouse glioma cells line GL261 and mouse microglia cell line BV2 were chosen in this studys. Firstly, Circadian genes expressions in glioma cells among M1 and M2 microglia, were detected, and unpolarized and M2 microglia exosomes were extracted. Subsequently, we labeled exosomes with PKH-67 and treated them with GL261 cells to observe the exosomes distribution. The GL261 cells phenotype and related protein expression were detected to explore the promotion effect of M2 microglial exosomes on gliomas. Then the miR-7239-3p specific inhibitors was added to vertify miR-7239-3p functions. Finally, we used a mouse subcutaneous tumorigenic model to verify the tumorigenic effect of M2 microglial exosomes in vivo. Results In the glioma co-cultured with M2 microglia, the expression of BMAL1 protein was decreased ( p <0.01) and the expression of CLOCK protein was increased ( p <0.05), which is in contrast to the gliomas co-cultured with M1 microglial. After treated by M2 microglia exosomes, the apoptosis of GL261 cells decreased ( p <0.001), and cell viability, proliferation and migration of GL261 cell increased. The expression of N-cadherin and Vimentin increased, and E-cadherin decreased after treated by M2 microglia exosomes. When added miR-7239-3p inhibitors to M2 microglia exosomes the aforementioned results were reversed. Conclusions We found that miR-7239-3p in the glioma microenvironment is recruited to glioma cells by exosomes and inhibited Bmal1 expression. M2 microglial exosomes promote the proliferation and migration of gliomas by regulating tumor-related protein expression and reducing apoptosis.