Development of a novel treatment for canine hemangiosarcoma using RNase-resistant microRNAs.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K05916
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 42020:Veterinary medical science-related
• Research Institution: Gifu University
• Principal Investigator: Mori Takashi 岐阜大学, 応用生物科学部, 教授 (40402218)
• Co-Investigator(Kenkyū-buntansha): 酒井 洋樹 岐阜大学, 応用生物科学部, 教授 (40283288)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: microRNA / RNase rasistance / angiosarcoma

Outline of Final Research Achievements

Synthetic miR-214 (miR-214/5AE), which showed higher cytotoxicity and greater nuclease resistance than mature miR-214, has been developed for clinical application. 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. 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.

Free Research Field

獣医臨床腫瘍学

Academic Significance and Societal Importance of the Research Achievements

RNA製剤開発におけるハードルのひとつは，生体内でのRNaseによる失活である。本研究で人工合成したmiR-214/5AEはRNase耐性を示すことから，生体内投与による効果が期待される。本研究で用いるアミノエチル基およびO-メチル基による化学修飾およびPassenger鎖の 塩基配列の改変は、他のmiRNAにも応用可能である。そのため、本研究結果は他の疾患でのmiRNAを用いた治療に応用することができるため、その意義は大きい。