TY - JOUR
T1 - Imatinib induces demethylation of miR-203 gene
T2 - An epigenetic mechanism of anti-tumor effect of imatinib
AU - Shibuta, Tatsuki
AU - Honda, Emi
AU - Shiotsu, Hiromichi
AU - Tanaka, Yuka
AU - Vellasamy, Shalini
AU - Shiratsuchi, Motoaki
AU - Umemura, Tsukuru
N1 - Funding Information:
This work was supported in part by a research grant (Grant No. 21659240 ) and a grant for “Invitation Program for East Asian Young Researchers”, from the Japan Society for the Promotion of Science (JSPS) .
Funding Information:
We appreciate the technical support from the Research Support Center, Graduate School of Medical Sciences, Kyushu University.
PY - 2013/10
Y1 - 2013/10
N2 - 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.
AB - 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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U2 - 10.1016/j.leukres.2013.07.019
DO - 10.1016/j.leukres.2013.07.019
M3 - Article
C2 - 23953880
AN - SCOPUS:84883561421
SN - 0145-2126
VL - 37
SP - 1278
EP - 1286
JO - Leukemia Research
JF - Leukemia Research
IS - 10
ER -
