Open AccessMicroRNA-29a-3p delivery via exosomes derived from engineered human mesenchymal stem cells exerts tumour suppressive effects by inhibiting migration and vasculogenic mimicry in glioma
Author(s) -
Zongpu Zhang,
Xing Guo,
Xiaofan Guo,
Rui Yu,
Mingyu Qian,
Shaobo Wang,
Xiao Gao,
Wei Qiu,
Qindong Guo,
Jianye Xu,
Zihang Chen,
Huizhi Wang,
Yanhua Qi,
Rongrong Zhao,
Hao Xue,
Gang Li
Publication year - 2021
Publication title -
aging
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.473
H-Index - 90
ISSN - 1945-4589
DOI - 10.18632/aging.202424
Subject(s) - vasculogenic mimicry , microvesicles , mesenchymal stem cell , glioma , angiogenesis , cancer research , microrna , exosome , biology , stem cell , microbiology and biotechnology , cell migration , immunology , in vitro , chemistry , cancer , metastasis , biochemistry , genetics , gene
Vasculogenic mimicry (VM), the formation of an alternative microvascular circulation independent of VEGF-driven angiogenesis, is reluctant to anti-angiogenesis therapy for glioma patients. However, treatments targeting VM are lacking due to the poor understanding of the molecular mechanism involved in VM formation. By analysing the TCGA database, microRNA-29a-3p (miR-29a-3p) was found to be highly expressed in normal brain tissue compared with glioma. An in vitro study revealed an inhibitory role for miR-29a-3p in glioma cell migration and VM formation, and further study confirmed that ROBO1 is a direct target of miR-29a-3p. Based on this, we engineered human mesenchymal stem cells (MSCs) to produce miR-29a-3p-overexpressing exosomes. Treatment with these exosomes attenuated migration and VM formation in glioma cells. Moreover, the anti-glioma role of miR-29a-3p and miR-29a-3p-overexpressing exosomes were confirmed in vivo . Overall, the present study demonstrates that MSCs can be used to produce miR-29a-3p-overexpressing exosomes, which have great potential for anti-VM therapy and may act as supplements to anti-angiogenetic therapy in the clinic.