Therapeutic applications of local injection of hsa-miR-634 into canine spontaneous malignant melanoma tumors
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 (...
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Veröffentlicht in: | Cancer gene therapy 2023-11, Vol.30 (11), p.1524-1529 |
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Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | 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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ISSN: | 0929-1903 1476-5500 |
DOI: | 10.1038/s41417-023-00656-5 |