Research Paper|Volume 13, Issue 15|pp 19243—19259

Glioma stem cell-derived exosomal miR-944 reduces glioma growth and angiogenesis by inhibiting AKT/ERK signaling

Jianxin Jiang¹, Jun Lu¹, Xiaolin Wang¹, Bing Sun¹, Xiaoxing Liu¹, Yasuo Ding¹, Guangzhong Gao¹

¹Department of Neurosurgery, Taizhou People’s Hospital, Taizhou 225300, Jiangsu, P.R. China

* Equal contribution

# Co-first author

Received: December 23, 2020Accepted: May 13, 2021Published: July 7, 2021

https://doi.org/10.18632/aging.203243

Copyright: © 2021 Jiang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

In this study, we investigated the regulatory role of exosomal microRNA-944 (miR-944) derived from glioma stem cells (GSCs) in glioma progression and angiogenesis. Bioinformatics analysis showed that miR-944 levels were significantly lower in high-grade gliomas (HGGs) than low-grade gliomas in the Chinese Glioma Genome Atlas and The Cancer Genome Atlas datasets. The overall survival rates were significantly shorter for glioma patients expressing low miR-944 levels than high miR-944 levels. GSC-derived exosomal miR-944 significantly decreased in vitro proliferation, migration, and tube formation by human umbilical vein endothelial cells (HUVECs). Targetscan and dual luciferase reporter assays demonstrated that miR-944 directly targets the 3’UTR of VEGFC. In vivo mouse studies demonstrated that injection of agomiR-944 directly into tumors 3 weeks after xenografting glioma cells significantly reduced tumor growth and angiogenesis. GSC-derived exosomal miR-944 significantly reduced VEGFC levels and suppressed activation of AKT/ERK signaling pathways in HUVECs and xenograft glioma cell tumors. These findings demonstrate that GSC-derived exosomal miR-944 inhibits glioma growth, progression, and angiogenesis by suppressing VEGFC expression and inhibiting the AKT/ERK signaling pathway.