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Therapeutic applications of local injection of hsa-miR-634 into canine spontaneous malignant melanoma tumors

Cancer Gene Therapy volume 30, pages 1524–1529 (2023)Cite this article

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Abstract

Malignant melanoma (MM) is one of the most common tumors in both dogs and humans. As canine MM (CMM) and human MM (HMM) have similar clinical characteristics, CMM appears to be a good clinical model for HMM. We previously demonstrated that the introduction of a synthetic double-strand-microRNA-634 (miR-634) mimic triggered apoptotic cell death by directly targeting the genes associated with cytoprotective processes in various human cancer cell lines, including those of HMM. This study aimed to investigate the antitumor effects of the local administration of miR-634 on spontaneous CMMs to provide a basis for future applications of miR-634 formulations in HMM treatment. We found that miR-634 administration induced apoptosis in CMM cell lines in vitro via downregulation of Asct2, Nrf2, and survivin expression, similar to the mechanisms in HMM cell lines. Furthermore, intratumoral miR-634 administration induced antitumor effects in four of seven spontaneous CMM cases, with no adverse effects. Local administration of miR-634 to lung metastasis under ultrasound guidance induced tumor shrinkage. These results confirm the antitumor effect of the local administration of miR-634 in spontaneous CMM, a model for spontaneous HMM, thereby providing a novel treatment strategy for HMM.

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Fig. 1: Antitumor activity of miR-634 in spontaneous canine malignant melanomas.
Fig. 2: Induction of apoptosis by miR-634 overexpression in canine melanoma cells.
Fig. 3: Delivery of miR-634 into tumor cells.

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Data availability

All data generated or analyzed during this study are included in this published article and its Supplementary Information files.

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Acknowledgements

This study was supported by Nanken-Kyoten, Tokyo Medical and Dental University. The authors thank Editage (www.editage.jp) for English language editing of this manuscript.

Funding

This work was funded in part by Grants-in-Aid for Scientific Research (21H02781 to J Inoue and 18H02688 to J Inazawa); a Grant-in-Aid for Scientific Research on Innovative Areas “Conquering cancer through NEO-dimensional systems understandings” (15H05908 to J Inazawa) from JSPS and MEXT, a research program of the Project for Cancer Research and Therapeutic Evolution (P-CREATE); and the Tailor-Made Medical Treatment with the BioBank Japan Project (BBJ) from the Japan Agency for Medical Research and Development (AMED).

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Authors and Affiliations

  1. Animal Medical Center, Gifu University, Gifu, Japan

    Ryutaro Yoshikawa, Ryota Iwasaki, Mitsuhiko Terauchi, Maya Ohta, Tomomi Hasegawa & Takashi Mori

  2. Department of Molecular Cytogenetics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan

    Jun Inoue & Johji Inazawa

  3. Joint Department of Veterinary Medicine Gifu University, Gifu, Japan

    Ryota Iwasaki & Takashi Mori

  4. Joint Graduate School of Veterinary Sciences, Gifu University, Gifu, Japan

    Yuji Fujii, Rui Mizuno & Takashi Mori

  5. Research Core Center, Tokyo Medical and Dental University, Tokyo, Japan

    Johji Inazawa

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  1. Ryutaro Yoshikawa
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Contributions

Conception and design: TM, J Inoue, J Inazawa; development of methodology: TM, J Inoue, J Inazawa; acquisition of data (provided animals, acquired and managed cases, provided facilities, etc.): RY, J Inoue., RI, MT, YF, MO, TH, RM; analysis and interpretation of data (statistical analysis, biostatistics, and computational analysis): RY, J Inazawa; writing, review, and/or revision of the manuscript: RY, J Inoue, RI, MT, YF, MO, TH, RR, TM, J Inazawa; administrative, technical, or material support (i.e., reporting or organizing data and constructing databases): J Inoue, TM, J Inazawa; study supervision: J Inoue, TM, J Inazawa.

Corresponding author

Correspondence to Ryutaro Yoshikawa.

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Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

The Ethics Review Board of the Joint Faculty of Veterinary Medicine of Gifu University approved this study (approval no.: E18009). Written informed consent was obtained from all dog owners. All experimental methods were performed in accordance with the ARRIVE guidelines. All methods were carried out in accordance with relevant national guidelines and regulations.

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Yoshikawa, R., Inoue, J., Iwasaki, R. et al. Therapeutic applications of local injection of hsa-miR-634 into canine spontaneous malignant melanoma tumors. Cancer Gene Ther 30, 1524–1529 (2023). https://doi.org/10.1038/s41417-023-00656-5

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