RRC ID |
44595
|
Author |
Shibuta T, Honda E, Shiotsu H, Tanaka Y, Vellasamy S, Shiratsuchi M, Umemura T.
|
Title |
Imatinib induces demethylation of miR-203 gene: an epigenetic mechanism of anti-tumor effect of imatinib.
|
Journal |
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.
|
Volume |
37(10)
|
Pages |
1278-86
|
Published |
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
|
Times Cited |
27
|
WOS Category
|
ONCOLOGY
HEMATOLOGY
|
Resource |
Human and Animal Cells |
KU812(RCB0495) |