Myc induced miR-144/451 contributes to the acquired imatinib resistance in chronic myelogenous leukemia cell K562

Biochem Biophys Res Commun. 2012 Aug 24;425(2):368-73. doi: 10.1016/j.bbrc.2012.07.098. Epub 2012 Jul 27.

Abstract

Imatinib resistance remains the big hurdle for CML therapy. Previous study reveals that c-myc is important for bcr-abl CML cell proliferation, while its role in imatinib resistance is largely unknown. In this study, we first found that c-myc expression is upregulated in imatinib resistant K562R cells, which in turn enhances the expression of miR-144/451. Knockdown of c-myc or restoration of miR-144/451 in the K562R cells sensitizes K562R cells to imatinib therapy. Our study here reveals an regulatory pathway between myc and miR-144/451 and highlights that targeting either myc or miR-144/451 might be valuable for eliminating the imatinib resistant CML cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Benzamides
  • Drug Resistance, Neoplasm / genetics*
  • Gene Knockdown Techniques
  • Humans
  • Imatinib Mesylate
  • K562 Cells
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Piperazines / therapeutic use*
  • Proto-Oncogene Proteins c-myc / genetics
  • Pyrimidines / therapeutic use*

Substances

  • Antineoplastic Agents
  • Benzamides
  • MIRN144 microRNA, human
  • MIRN451 microRNA, human
  • MicroRNAs
  • Piperazines
  • Proto-Oncogene Proteins c-myc
  • Pyrimidines
  • Imatinib Mesylate