Laboratory of Molecular Diagnostic and Therapeutics, Joint faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi, Japan.
The United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu, Japan.
Vet Comp Oncol. 2016 Dec;14(4):384-394. doi: 10.1111/vco.12118. Epub 2014 Oct 3.
MicroRNA (miR)-203 is downregulated and acts as an anti-oncomir in melanoma cells. Here, using human and canine melanoma cells, we elucidated the effects of miR-203 on cyclic adenosine monophosphate response element binding protein (CREB)/microphthalmia-associated transcription factor (MITF)/RAB27a pathway, which is known to be important for the development and progression of human melanoma. In this study, we showed that miR-203 directly targeted CREB1 and regulated its downstream targets, MITF and RAB27a. miR-203 significantly suppressed the growth of human and canine melanoma cells and inhibited melanosome transport through the suppression of the signalling pathway. In conclusion, miR-203 was shown to be a common tumour-suppressive miRNA in human and canine melanoma and thus to play a crucial role in the biological mechanisms of melanoma development.
微小 RNA（miR）-203 在黑色素瘤细胞中下调并作为一种抑癌 miRNA 发挥作用。在这里，我们使用人源和犬源黑色素瘤细胞，阐明了 miR-203 对环磷酸腺苷反应元件结合蛋白（CREB）/小眼畸形相关转录因子（MITF）/RAB27a 通路的影响，该通路已知对人类黑色素瘤的发生和进展很重要。在这项研究中，我们表明 miR-203 可以直接靶向 CREB1 并调节其下游靶标 MITF 和 RAB27a。miR-203 显著抑制了人源和犬源黑色素瘤细胞的生长，并通过抑制信号通路抑制黑素体运输。总之，miR-203 被证明是人类和犬源黑色素瘤中一种常见的肿瘤抑制 miRNA，因此在黑色素瘤发生的生物学机制中发挥着关键作用。
