恶性黑素瘤（MM）是狗和人类最常见的肿瘤之一。由于犬恶性黑素瘤（CMM）和人类恶性黑素瘤（HMM）具有相似的临床特征，CMM似乎是HMM的良好临床模型。我们先前证明，合成的双链微小RNA-634（miR-634）模拟子的引入通过直接靶向与胞内保护过程相关的基因，在包括HMM在内的各种人类癌细胞系中触发了细胞凋亡。本研究旨在研究miR-634局部给药对自发性CMM的抗肿瘤效果，为将miR-634制剂用于HMM治疗提供基础。我们发现，miR-634给药通过下调Asct2、Nrf2和survivin的表达，在体外引起CMM细胞系的凋亡，与HMM细胞系的机制类似。此外，肿瘤局部给药miR-634在七例自发性CMM中的四例中诱导了抗肿瘤效果，且没有不良反应。在超声引导下，miR-634局部给药使肺转移瘤缩小。这些结果确认了miR-634局部给药在自发性CMM中的抗肿瘤效果，为自发性HMM模型提供了一种新的治疗策略。© 2023. 作者（s）在Springer Nature America, Inc.的独家授权下发布。

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.© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.