Focused ultrasound combined with miR-1208-equipped exosomes inhibits malignant progression of glioma.

Abstract

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.

• Authors: Ying Zhan, Yichen Song, Wei Qiao, Lu Sun, Xin Wang, Bolong Yi, Xinyu Yang, Lian Ji, Peng Su, Wujun Zhao, Zhijun Liu, Weidong Ren
• Journal: British journal of cancer (Br J Cancer) Vol. 129 Issue 7 Pg. 1083-1094 (10 2023) ISSN: 1532-1827 [Electronic] England
• PMID: 37580442 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2023. The Author(s), under exclusive licence to Springer Nature Limited.

Chemical References

• IGF2BP2 protein, human
• Methyltransferases
• METTL3 protein, human
• MicroRNAs
• RNA-Binding Proteins
• MIRN1208 microRNA, human

Topics

• Humans
• Blood-Brain Barrier (metabolism)
• Exosomes (metabolism)
• Glioma (genetics, therapy, metabolism)
• Mesenchymal Stem Cells (metabolism)
• Methyltransferases
• MicroRNAs (genetics, metabolism)
• RNA-Binding Proteins (metabolism)