1. Imatinib induces demethylation of miR-203 gene: an epigenetic mechanism of anti-tumor effect of imatinib.
- Author
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Shibuta T, Honda E, Shiotsu H, Tanaka Y, Vellasamy S, Shiratsuchi M, and Umemura T
- Subjects
- Cell Line, Tumor, CpG Islands, DNA (Cytosine-5-)-Methyltransferase 1, DNA (Cytosine-5-)-Methyltransferases genetics, DNA (Cytosine-5-)-Methyltransferases metabolism, Fusion Proteins, bcr-abl genetics, Fusion Proteins, bcr-abl metabolism, Gene Expression Profiling, Gene Expression Regulation, Leukemic drug effects, Humans, Imatinib Mesylate, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics, Leukemia, Myelogenous, Chronic, BCR-ABL Positive metabolism, MicroRNAs metabolism, Promoter Regions, Genetic, RNA, Messenger genetics, RNA, Messenger metabolism, DNA Methyltransferase 3B, Antineoplastic Agents pharmacology, Benzamides pharmacology, DNA Methylation drug effects, Epigenesis, Genetic drug effects, MicroRNAs genetics, Piperazines pharmacology, Protein Kinase Inhibitors pharmacology, Pyrimidines pharmacology
- 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., (Copyright © 2013 Elsevier Ltd. All rights reserved.)
- Published
- 2013
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