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Human marrow stromal cells secrete microRNA-375-containing exosomes to regulate glioma progression

Cancer Gene Therapy volume 27, pages 203–215 (2020)Cite this article

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Abstract

It is well established that human marrow stromal cells (hMSCs) can directly migrate towards tumor microenvironments associated with tumor formation and intracellular communication. Gene regulatory networks in tumors may be targeted by microRNAs (miRNAs), especially those derived in exosomes from hMSCs. However, the potential functional roles of hMSCs in glioma cell growth still remain controversial. Therefore, this study aimed at exploring the regulatory mechanisms of hMSC exosomal microRNA-375 (miR-375) in glioma. Microarray analysis was used to initially screen out glioma-related genes. The interaction between miR-375 and solute carrier family 31 member 1 (SLC31A1) was confirmed by dual-luciferase reporter gene assay. miR-375 and SLC31A1 expression in glioma cells were determined. Glioma cells were initially exposed to exosomes derived from hMSCs treated with miR-375. Subsequently, the rates of proliferation, migration, invasion and apoptosis were determined in glioma cells using in vitro assays. The effects of exosomal miR-375 from hMSCs on tumor growth in vivo were also measured using xenograft tumor in nude mice. We found that miR-375 and SLC31A1 showed significantly lower and higher expression of glioma cells respectively. Additionally, restored miR-375 expression resulted in suppressed cell proliferation, migration and invasion, and increased apoptosis by targeting SLC31A1. Next, in vitro experiments demonstrated that hMSC-derived exosomes overexpressing miR-375 promoted apoptosis while suppressing proliferation, migration and invasion. Furthermore, in vivo experiments confirmed the negative regulatory effects of hMSC-derived exosomes with overexpressed miR-375. We conclude that exosomal miR-375 from hMSCs inhibits glioma cell progression through SLC31A1 suppression, and ultimately serves as a potential target in the treatment of gliomas.

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Acknowledgements

We would like show sincere appreciation to the reviewers for critical comments on this article.

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  1. These authors contributed equally: Sheng-Ze Deng, Min-Fang Lai

Authors and Affiliations

  1. Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, People’s Republic of China

    Sheng-Ze Deng, You-Ping Li, Chun-Hua Xu, Hao-Ran Zhang & Jian-Guo Kuang

  2. Department of Pharmacy, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, People’s Republic of China

    Min-Fang Lai

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Correspondence to Jian-Guo Kuang.

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This study was carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The study was consistent with the principles used to relieve the pains of animals as well as using the least number of animals as possible.

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Deng, SZ., Lai, MF., Li, YP. et al. Human marrow stromal cells secrete microRNA-375-containing exosomes to regulate glioma progression. Cancer Gene Ther 27, 203–215 (2020). https://doi.org/10.1038/s41417-019-0079-9

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