Abstract
Canine hemangiosarcoma (HSA) has an extremely poor prognosis, making it necessary to develop new systemic treatment methods. MicroRNA-214 (miR-214) is one of many microRNAs (miRNA) that can induce apoptosis in HSA cell lines. Synthetic miR-214 (miR-214/5AE), which showed higher cytotoxicity and greater nuclease resistance than mature miR-214, has been developed for clinical application. In this study, we evaluated the effects of miR-214/5AE on stage 2 HSA in a mouse model. Mice intraperitoneally administered with miR-214/5AE (5AE group) had significantly fewer intraperitoneal dissemination tumor foci (median number: 72.5 vs. 237.5; p < 0.05) and a lower median foci weight (0.26 g vs. 0.61 g; p < 0.05). Mice in the 5AE group had increased expression of p53 and cleaved caspase-3, and a significantly lower proportion of Ki-67-positive cells, than those in the non-specific miR group. Notably, no significant side effects were observed. These results indicate that intraperitoneal administration of miR-214/5AE exhibits antitumor effects in an intraperitoneal dissemination mouse model of HSA by inducing apoptosis and suppressing cell proliferation. These results provide a basis for future studies on the antitumor effect of miR-214/5AE for HSA.
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The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
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Conception and Design: Ryutaro Yoshikawa, Yoshihito Ueno, Takashi Mori.
Acquisition of Data: Ryutaro Yoshikawa, Atsushi Maeda, Hiroki Sakai, Shintaro Kimura, Tomohiro Sawadaishi, Satoru Kohgo, Kohei Yamada.
Analysis and Interpretation of Data: Ryutaro Yoshikawa, Atsushi Maeda, Hiroki Sakai, Shintaro Kimura, Tomohiro Sawadaishi, Satoru Kohgo, Kohei Yamada.
Drafting the Article: Ryutaro Yoshikawa.
Revising Article for Intellectual Content: Atsushi Maeda, Yoshihito Ueno, Hiroki Sakai, Shintaro Kimura, Tomohiro Sawadaishi, Satoru Kohgo, Kohei Yamada, Takashi Mori.
Final Approval of the Completed Article: Ryutaro Yoshikawa, Atsushi Maeda, Yoshihito Ueno, Hiroki Sakai, Shintaro Kimura, Tomohiro Sawadaishi, Satoru Kohgo, Kohei Yamada, Takashi Mori.
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The protocol of animal experiments was reviewed and approved by the Ethics Review Board of the Joint Faculty of Veterinary Medicine of Gifu University (approval number: 2019–117).
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Yoshikawa, R., Maeda, A., Ueno, Y. et al. Intraperitoneal administration of synthetic microRNA-214 elicits tumor suppression in an intraperitoneal dissemination mouse model of canine hemangiosarcoma. Vet Res Commun 46, 447–457 (2022). https://doi.org/10.1007/s11259-021-09869-1
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DOI: https://doi.org/10.1007/s11259-021-09869-1