Imatinib induces demethylation of miR-203 gene: An epigenetic mechanism of anti-tumor effect of imatinib |
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| Authors: | Tatsuki Shibuta Emi Honda Hiromichi Shiotsu Yuka Tanaka Shalini Vellasamy Motoaki Shiratsuchi Tsukuru Umemura |
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| Affiliation: | 1. Department of Health Sciences, Faculty of Medical Sciences, Graduate School of Medical Sciences, Kyushu University, Japan;2. Department of Medicine and Bioregulatory Science, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan;3. Department of Pathology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Malaysia |
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| Abstract: | MicroRNA (miRNA) is an important regulator of cellular proliferation, differentiation and death. Leukemia-specific signature of miRNAs suggests that epigenetic dysregulation of miRNAs is important for leukemogenesis. We focused on the role of DNA methylation of miR-203 which targets BCR-ABL1 mRNA. The microarray analysis showed that 48 miRNAs of CpG-rich 212 miRNAs were upregulated over 2-fold after imatinib treatment. Imatinib induced the demethylation of the miR-203 promoter region, resulting in low expression of targeted BCR-ABL1 gene, and loss of proliferation of leukemic cells. In conclusion, demethylation of miR-203 is one of the molecular mechanisms of imatinib-induced inhibition of BCR-ABL1-positive leukemic cells. |
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| Keywords: | CML MicroRNA miR-203 Methylation DNA methyltransferase |
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