Imatinib induces demethylation of miR-203 gene: An epigenetic mechanism of anti-tumor effect of imatinib

Tatsuki Shibuta, Emi Honda, Hiromichi Shiotsu, Yuka Tanaka, Shalini Vellasamy, Motoaki Shiratsuchi, Tsukuru Umemura

Research output: Contribution to journalArticle

28 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1278-1286
Number of pages9
JournalLeukemia Research
Volume37
Issue number10
DOIs
Publication statusPublished - Oct 2013

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology
  • Cancer Research

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