Inhibition of BCR/ABL protein expression by miR-203 sensitizes for imatinib mesylate

PLoS One. 2013 Apr 16;8(4):e61858. doi: 10.1371/journal.pone.0061858. Print 2013.

Abstract

Selective inhibition of BCR/ABL expression by RNA interference has been demonstrated as an effective strategy in CML treatment and a reversal to imatinib resistance. microRNAs (miRNAs) are small regulatory RNAs involved in post-transcriptional gene regulation. miR-203 is supposed to directly regulate ABL and BCR/ABL expression, however, the role of miR-203 in imatinib-resistant cells is not clear. Here, we report that overexpression of miR-203 in BaF3-BCR/ABL cells with T315I mutant inhibited cell growth and colony formation ability. Furthermore, miR-203 increased sensitivity to imatinib in BaF3-BCR/ABL(T315I) cells, thereby antagonizing the main mechanism of resistance to imatinib.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Benzamides / pharmacology*
  • Blotting, Western
  • Cell Cycle / drug effects
  • Cell Cycle / genetics
  • Cell Proliferation / drug effects
  • Female
  • Fusion Proteins, bcr-abl / genetics
  • Fusion Proteins, bcr-abl / metabolism*
  • Humans
  • Imatinib Mesylate
  • Male
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Piperazines / pharmacology*
  • Pyrimidines / pharmacology*
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Benzamides
  • MIRN203 microRNA, human
  • MicroRNAs
  • Piperazines
  • Pyrimidines
  • Imatinib Mesylate
  • Fusion Proteins, bcr-abl

Grants and funding

This work was supported by the Doctor Foundation of school of Medical Lab Science, Chongqing Medical University to Yajuan Li. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.