DNA methylation contributes toward silencing of antioncogenic microRNA-203 in human and canine melanoma cells. Issue 5 (October 2015)

• Record Type: Journal Article
• Authors: Noguchi, Shunsuke; Mori, Takashi; Nakagawa, Takayuki; Itamoto, Kazuhito; Haraguchi, Tomoya; Mizuno, Takuya
• Is Part Of: Melanoma research. Volume 25:Issue 5(2015)
• Publication Date: 2015-10
• Subjects: Melanoma -- Periodicals; Melanoma -- Periodicals; Melanomen; 616.99477
• DOI: 10.1097/CMR.0000000000000183
• Languages: English
• ISSNs: 0960-8931

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <p>Melanoma is a poor-prognosis cancer in both humans and dogs. We have elucidated the antitumor mechanisms of antioncogenic microRNA (miR)-203 which is downregulated in human melanoma, as well as in canine melanoma. The aim of this study was to clarify the mechanism of this downregulation. We focused on epigenetic aberration of miR-203 transcription. Treatment with 5-aza-2′-deoxycitidine (5-aza) markedly upregulated the expression level of miR-203 in almost all of the cell lines tested. Furthermore, bisulfite sequencing or methylation-specific PCR showed DNA methylation of CpG islands upstream of the miR-203 coding region (<italic>MIR203</italic>) in both human and canine melanoma cells, as well as in canine clinical specimens, but not in human normal melanocytes. The results of a luciferase activity assay showed obvious suppression of the transcription of miR-203 by DNA methylation. The use of the luciferase activity assay for <italic>CREB1</italic> and an inhibition assay of miR-203 function performed with an miR-203 inhibitor confirmed the contribution of miR-203 upregulation toward the negative regulation of the target gene of miR-203. These results indicate that canine melanoma might be a preclinical model of human melanoma for epigenetic studies. In addition, this study suggests that agents that can demethylate <italic>MIR203</italic> could be a common promising therapeutic agent for the treatment of human and canine melanomas.</p> </sec> </abstract>