Involvement of miR-21 in resistance to daunorubicin by regulating PTEN expression in the leukaemia K562 cell line

FEBS Lett. 2011 Jan 21;585(2):402-8. doi: 10.1016/j.febslet.2010.12.027. Epub 2010 Dec 25.

Abstract

Recent studies have shown microRNA-21 (miR-21) is overexpressed in several types of cancer and contributes to tumor resistance to chemotherapy. In this study, we investigated whether miR-21 mediated resistance of the leukaemia cell line K562 to the chemotherapeutic agent daunorubicin (DNR). miR-21 expression was upregulated in the DNR resistant cell line K562/DNR compared to its parental line K562. Stable transfection of miR-21 induced drug resistance in K562, while suppression of miR-21 in K562/DNR led to enhanced DNR cytotoxicity. Additional experiments indicate that the mechanism of miR-21 drug resistance involves the PI3K/Akt pathway and changes following PTEN protein expression. This study provides a novel mechanism for understanding leukaemia drug resistance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Daunorubicin / pharmacology*
  • Drug Resistance, Neoplasm*
  • Gene Expression Regulation, Leukemic*
  • Humans
  • K562 Cells
  • Leukemia / drug therapy
  • Leukemia / pathology*
  • MicroRNAs / physiology*
  • PTEN Phosphohydrolase / genetics*
  • PTEN Phosphohydrolase / pharmacokinetics
  • PTEN Phosphohydrolase / physiology
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism

Substances

  • Antineoplastic Agents
  • MIRN21 microRNA, human
  • MicroRNAs
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • Daunorubicin