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

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.
AuthorsRyutaro Yoshikawa, Jun Inoue, Ryota Iwasaki, Mitsuhiko Terauchi, Yuji Fujii, Maya Ohta, Tomomi Hasegawa, Rui Mizuno, Takashi Mori, Johji Inazawa
JournalCancer gene therapy (Cancer Gene Ther) Vol. 30 Issue 11 Pg. 1524-1529 (Nov 2023) ISSN: 1476-5500 [Electronic] England
PMID37553484 (Publication Type: Journal Article)
Copyright© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.
Chemical References
  • MIRN-634 microRNA, human
  • MicroRNAs
Topics
  • Humans
  • Dogs
  • Animals
  • Cell Line, Tumor
  • Melanoma (drug therapy, genetics)
  • MicroRNAs (genetics, metabolism)
  • Gene Expression Regulation, Neoplastic
  • Cell Proliferation (genetics)

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