Exosomes derived from microRNA-199a-overexpressing mesenchymal stem cells inhibit glioma progression by down-regulating AGAP2

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.