title: Imatinib induces demethylation of miR-203 gene: an epigenetic mechanism of anti-tumor effect of imatinib.
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.
authors: Department of Health Sciences, Faculty of Medical Sciences, Graduate School of Medical Sciences, Kyushu University, Japan.
authors: Tatsuki
authors: T
authors: Shibuta
authors: Emi
authors: E
authors: Honda
authors: Hiromichi
authors: H
authors: Shiotsu
authors: Yuka
authors: Y
authors: Tanaka
authors: Shalini
authors: S
authors: Vellasamy
authors: Motoaki
authors: M
authors: Shiratsuchi
authors: Tsukuru
authors: T
authors: Umemura
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology*; D045744:Cell Line, Tumor; D018899:CpG Islands; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects*; D044127:Epigenesis, Genetic / Q000187:drug effects*; D016044:Fusion Proteins, bcr-abl / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000097584:DNA Methyltransferase 3B
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D016044:Fusion Proteins, bcr-abl; D000068877:Imatinib Mesylate; D035683:MicroRNAs; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D012333:RNA, Messenger; D000097584:DNA Methyltransferase 3B; C546703:MIRN203 microRNA, human
keywords: CML; DNA methyltransferase; Methylation; MicroRNA; miR-203