Focused ultrasound combined with miR-1208-equipped exosomes inhibits malignant progression of glioma
Menée à l'aide de 8 échantillons de tissus cérébraux sains, de 56 échantillons de gliomes et d'une xénogreffe sur un modèle murin, cette étude met en évidence l'intérêt d'un traitement combinant ultrasons focalisés et exosomes chargés en microARN miR-1208 pour inhiber la progression tumorale
Background : Exosomes (Exos) can safely and effectively deliver therapeutic substances to glioma cells; however, their blood–brain barrier (BBB) crossing capacity remains limited. Focused ultrasound (FUS) can transiently, reversibly, and locally open the BBB, while the effects of FUS combined with Exos-miRNA on the treatment of glioma have not been explored to date. Methods : Exos were extracted by differential centrifugation and the efficacy of miR-1208-loaded Exos combined with FUS in the treatment of glioma was detected by CCK-8, colony formation, flow cytometry, transwell and tumour xenografts assays. The METTL3-mediated regulation of IGF2BP2 on mRNA stability of NUP214 was determined by MeRIP-qPCR, half-life and RIP assays. Results : We used Exos secreted by mesenchymal stem cells as carriers for the tumour suppressor gene miR-1208, and following FUS irradiation, more Exos carrying miR-1208 were allowed to pass through the BBB, and the uptake of miR-1208 in Exos by glioma cells was promoted, thereby achieving high-efficiency tumour-suppressive effects. Furthermore, the molecular mechanism underlying this effect was elucidated that miR-1208 downregulated the m6A methylation level of NUP214 mRNA by negatively regulating the expression of METTL3, thereby NUP214 expression and TGF-
β pathway activity were suppressed. Conclusions
:
MiR-1208-loaded Exos combined with FUS is expected to become an effective glioma treatment and deserves further clinical evaluation.