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Intraperitoneal administration of synthetic microRNA-214 elicits tumor suppression in an intraperitoneal dissemination mouse model of canine hemangiosarcoma

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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Contributions

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.

Corresponding author

Correspondence to Ryutaro Yoshikawa.

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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

Keywords

  • Antitumor
  • Canine hemangiosarcoma
  • Intraperitoneal dissemination mouse model
  • MicroRNA
  • miR-214/5AE