miR-34a contributes to megakaryocytic differentiation of K562 cells independently of p53

Blood. 2009 Sep 3;114(10):2181-92. doi: 10.1182/blood-2009-02-205062. Epub 2009 Jul 7.


The role of miRNAs in regulating megakaryocyte differentiation was examined using bipotent K562 human leukemia cells. miR-34a is strongly up-regulated during phorbol ester-induced megakaryocyte differentiation, but not during hemin-induced erythrocyte differentiation. Enforced expression of miR-34a in K562 cells inhibits cell proliferation, induces cell-cycle arrest in G(1) phase, and promotes megakaryocyte differentiation as measured by CD41 induction. miR-34a expression is also up-regulated during thrombopoietin-induced differentiation of CD34(+) hematopoietic precursors, and its enforced expression in these cells significantly increases the number of megakaryocyte colonies. miR-34a directly regulates expression of MYB, facilitating megakaryocyte differentiation, and of CDK4 and CDK6, to inhibit the G(1)/S transition. However, these miR-34a target genes are down-regulated rapidly after inducing megakaryocyte differentiation before miR-34a is induced. This suggests that miR-34a is not responsible for the initial down-regulation but may contribute to maintaining their suppression later on. Previous studies have implicated miR-34a as a tumor suppressor gene whose transcription is activated by p53. However, in p53-null K562 cells, phorbol esters induce miR-34a expression independently of p53 by activating an alternative phorbol ester-responsive promoter to produce a longer pri-miR-34a transcript.

MeSH terms

  • Antigens, CD34
  • Carcinogens / pharmacology
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology*
  • G1 Phase / drug effects
  • G1 Phase / physiology*
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / metabolism
  • Humans
  • K562 Cells
  • Megakaryocytes / cytology
  • Megakaryocytes / metabolism*
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • Phorbol Esters / pharmacology
  • Platelet Membrane Glycoprotein IIb / biosynthesis
  • Promoter Regions, Genetic / physiology
  • Proto-Oncogene Proteins c-myb / metabolism
  • Thrombopoietin / pharmacology
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*
  • Up-Regulation / drug effects
  • Up-Regulation / physiology*


  • Antigens, CD34
  • Carcinogens
  • MIRN34 microRNA, human
  • MicroRNAs
  • Phorbol Esters
  • Platelet Membrane Glycoprotein IIb
  • Proto-Oncogene Proteins c-myb
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Thrombopoietin