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Journal of Translational Medicine

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Open Access 01-12-2021 | Glioma | Research

M2 macrophage-derived exosomal microRNAs inhibit cell migration and invasion in gliomas through PI3K/AKT/mTOR signaling pathway

Authors: Jie Yao, Zefen Wang, Yong Cheng, Chao Ma, Yahua Zhong, Yilei Xiao, Xu Gao, Zhiqiang Li

Published in: Journal of Translational Medicine | Issue 1/2021

Abstract

Background

Glioma, the most common primary brain tumor, account Preparing figures for 30 to 40% of all intracranial tumors. Herein, we aimed to study the effects of M2 macrophage-derived exosomal microRNAs (miRNAs) on glioma cells.

Methods

First, we identified seven differentially expressed miRNAs in infiltrating macrophages and detected the expression of these seven miRNAs in M2 macrophages. We then selected hsa-miR-15a-5p (miR-15a) and hsa-miR-92a-3p (miR-92a) for follow-up studies, and confirmed that miR-15a and miR-92a were under-expressed in M2 macrophage exosomes. Subsequently, we demonstrated that M2 macrophage-derived exosomes promoted migration and invasion of glioma cells, while exosomal miR-15a and miR-92a had the opposite effects on glioma cells. Next, we performed the target gene prediction in four databases and conducted target gene validation by qRT-PCR, western blot and dual luciferase reporter gene assays.

Results

The results revealed that miR-15a and miR-92a were bound to CCND1 and RAP1B, respectively. Western blot assays demonstrated that interference with the expression of CCND1 or RAP1B reduced the phosphorylation level of AKT and mTOR, indicating that both CCND1 and RAP1B can activate the PI3K/AKT/mTOR signaling pathway.

Conclusion

Collectively, these findings indicate that M2 macrophage-derived exosomal miR-15a and miR-92a inhibit cell migration and invasion of glioma cells through PI3K/AKT/mTOR signaling pathway.

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Title: M2 macrophage-derived exosomal microRNAs inhibit cell migration and invasion in gliomas through PI3K/AKT/mTOR signaling pathway
Authors: Jie Yao
Zefen Wang
Yong Cheng
Chao Ma
Yahua Zhong
Yilei Xiao
Xu Gao
Zhiqiang Li
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Glioma
Glioma
Glioma
Published in: Journal of Translational Medicine / Issue 1/2021
Electronic ISSN: 1479-5876
DOI: https://doi.org/10.1186/s12967-021-02766-w

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