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Profile of miRNAs in small extracellular vesicles released from glioblastoma cells treated by boron neutron capture therapy

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Abstract

Purpose

Boron neutron capture therapy (BNCT) is a tumor cell-selective particle-radiation therapy. In BNCT, administered p-boronophenylalanine (BPA) is selectively taken up by tumor cells, and the tumor is irradiated with thermal neutrons. High-LET α-particles and recoil 7Li, which have a path length of 5–9 μm, are generated by the capture reaction between 10B and thermal neutrons and selectively kill tumor cells that have uptaken 10B. Although BNCT has prolonged the survival time of malignant glioma patients, recurrences are still to be resolved. miRNAs, that are encapsulated in small extracellular vesicles (sEVs) in body fluids and exist stably may serve critical role in recurrence. In this study, we comprehensively investigated microRNAs (miRNAs) in sEVs released from post-BNCT glioblastoma cells.

Method

Glioblastoma U87 MG cells were treated with 25 ppm of BPA in the culture media and irradiated with thermal neutrons. After irradiation, they were plated into dishes and cultured for 3 days in the 5% CO2 incubator. Then, sEVs released into the medium were collected by column chromatography, and miRNAs in sEVs were comprehensively investigated using microarrays.

Result

An increase in 20 individual miRNAs (ratio > 2) and a decrease in 2 individual miRNAs (ratio < 0.5) were detected in BNCT cells compared with non-irradiated cells. Among detected miRNAs, 20 miRNAs were associated with worse prognosis of glioma in Kaplan Meier Survival Analysis of overall survival in TCGA.

Conclusion

These miRNA after BNCT may proceed tumors, modulate radiation resistance, or inhibit invasion and affect the prognosis of glioma.

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Data availability

The datasets generated during this study are available in the Gene Expression Omnibus repository (accession number: GSE243221).

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Acknowledgements

This work was supported by the Extramural Collaboration Research Grant of the Brain Research Institute, Niigata University to N.K., Cancer Research Institute, Kanazawa University to N.K., and Japan Society for the Promotion of Science KAKENHI Grant Number 21K09151 to N.K.

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Authors and Affiliations

  1. Particle Radiation Oncology Research Center, Institute for Integrated Radiation and Nuclear Science, Kyoto University, 2-1010 Asashiro-Nishi, Kumatori, Sennan-gun, Osaka, 590-0494, Japan

    Natsuko Kondo, Yoshinori Sakurai & Minoru Suzuki

  2. Division of Radiation Biochemistry, Institute for Integrated Radiation and Nuclear Science, Kyoto University, 2-1010 Asashiro-Nishi, Kumatori, Sennan-gun, Osaka, 590-0494, Japan

    Tadatoshi Kinouchi

  3. Department of Neurosurgery, Brain Research Institute, Niigata University, Niigata, Japan

    Manabu Natsumeda & Masayasu Okada

  4. Division of Pharmacotherapeutics, Keio University Faculty of Pharmacy, Tokyo, Japan

    Juntaro Matsuzaki

  5. Division of Tumor Cell Biology and Bioimaging, Cancer Research Institute of Kanazawa University, Kanazawa, Japan

    Eishu Hirata

Authors
  1. Natsuko Kondo
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  2. Tadatoshi Kinouchi
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  3. Manabu Natsumeda
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  4. Juntaro Matsuzaki
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  5. Eishu Hirata
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  6. Yoshinori Sakurai
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  7. Masayasu Okada
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  8. Minoru Suzuki
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Contributions

Natsuko Kondo, Manabu Natsumeda and Eishu Hirata contributed to the study conception and design. Material preparation, data collection and analysis were performed by Natsuko Kondo, Tadatoshi Kinouchi, Yoshinori Sakurai and Juntaro Matsuzaki. The first draft of the manuscript was written by Natsuko Kondo and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Natsuko Kondo.

Ethics declarations

This work was supported by the Extramural Collaboration Research Grant of the Brain Research Institute, Niigata University to N.K., Cancer Research Institute, Kanazawa University to N.K., and Japan Society for the Promotion of Science KAKENHI Grant Number 21K09151 to N.K.

Competing interests

The authors declare no competing interests.

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Kondo, N., Kinouchi, T., Natsumeda, M. et al. Profile of miRNAs in small extracellular vesicles released from glioblastoma cells treated by boron neutron capture therapy. J Neurooncol (2024). https://doi.org/10.1007/s11060-024-04649-8

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