Abstract
Accumulating evidence has implied that microRNAs (miRNAs) are implicated in glioma progression, and genetically engineered mesenchymal stem cells can help to inhibit tumor growth of glioma. Herein we hypothesized that miR-199a could be delivered by mesenchymal stem cells to glioma cells through exosomes and thus prevent the glioma development by down-regulating ArfGAP with GTPase domain, ankyrin repeat and PH domain 2 (AGAP2). The expression pattern of miR-199a and AGAP2 was characterized in glioma tissues and cells using RNA polymerase chain reaction quantification, immunohistochemical staining and Western blot assays. Mesenchymal stem cells transfected with miR-199a mimic or their derived exosomes were co-cultured with U251 cells. The biological behaviors as well as chemosensitivity of U251 cells were assessed to explore the involvement of miR-199a/AGAP2 in glioma. MiR-199a was poorly expressed in glioma tissue and cells while AGAP2 was highly expressed. Mesenchymal stem cells delivered miR-199a to the glioma cells via the exosomes, which resulted in the suppression of the proliferation, invasion and migration of glioma cells. Besides, mesenchymal stem cells over-expressing miR-199a enhanced the chemosensitivity to temozolomide and inhibited the tumor growth in vivo. Taken together, mesenchymal stem cell-derived exosomal miR-199a can inhibit the progression of glioma by down-regulating AGAP2.
Highlights
Accompanied with a high mortality rate, gliomas are a type of brain and spinal cord tumor that originate from glia cells and can develop into malignant neoplasms [1, 2]
These results suggested that miR199a is likely to target the Arf GTPaseactivating protein-2 (AGAP2) gene in glioma via exosomes, which could prevent glioma development
We explored the role of mesenchymal stem cells (MSCs)-derived exosomes delivering miR-199a in gliomas
Summary
Accompanied with a high mortality rate, gliomas are a type of brain and spinal cord tumor that originate from glia cells and can develop into malignant neoplasms [1, 2]. Radiation therapy and chemotherapy are important methods for the management of patients with gliomas [3]. Due to the tendency of glioma cells to infiltrate the brain and migrate long distances from the tumor, it is impossible to rely on surgical resection to completely remove the tumour [4]. In recurrent high-grade gliomas, there are very few satisfactory treatment methods with a desirable prognosis [5]. MSCs can produce and secrete exosomes that can be useful and conducive in glioma treatment [8, 9]. It is promising to further explore a novel treatment of glioma based on MSCs-derived exosomes
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