RRC ID 44595
著者 Shibuta T, Honda E, Shiotsu H, Tanaka Y, Vellasamy S, Shiratsuchi M, Umemura T.
タイトル Imatinib induces demethylation of miR-203 gene: an epigenetic mechanism of anti-tumor effect of imatinib.
ジャーナル Leuk Res
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.
巻・号 37(10)
ページ 1278-86
公開日 2013-10-1
DOI 10.1016/j.leukres.2013.07.019
PII S0145-2126(13)00246-4
PMID 23953880
MeSH Antineoplastic Agents / pharmacology* Benzamides / pharmacology* Cell Line, Tumor CpG Islands DNA (Cytosine-5-)-Methyltransferase 1 DNA (Cytosine-5-)-Methyltransferases / genetics DNA (Cytosine-5-)-Methyltransferases / metabolism DNA Methylation / drug effects* Epigenesis, Genetic / drug effects* 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 / genetics* MicroRNAs / metabolism Piperazines / pharmacology* Promoter Regions, Genetic Protein Kinase Inhibitors / pharmacology* Pyrimidines / pharmacology* RNA, Messenger / genetics RNA, Messenger / metabolism
IF 2.214
引用数 27
WOS 分野 ONCOLOGY HEMATOLOGY
リソース情報
ヒト・動物細胞 KU812(RCB0495)