Targeting Smad4 links microRNA-146a to the TGF-beta pathway during retinoid acid induction in acute promyelocytic leukemia cell line

Int J Hematol. 2010 Jul;92(1):129-35. doi: 10.1007/s12185-010-0626-5. Epub 2010 Jun 25.


The expression pattern of microRNAs (miRNAs) and their potential target genes were investigated in acute promyelocytic leukemia (APL) cell line NB4 cells during all-trans-retinoid acid (ATRA) treatment by using a miRNA microarrays platform and real-time quantitative PCR (RTQ-PCR). MiR-146a as one of the miRNAs down-regulated by ATRA during APL differentiation was identified. Direct interaction between miR146a and its predictive target gene Smad4 were confirmed by Luciferase assay. Down-regulation of miR-146a and upregulation of Smad4 at protein levels were demonstrated. These data suggested that miR-146a might influence proliferation of APL cells through TGF-beta1/Smad signal transduction pathway during ATRA induction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Gene Expression Profiling
  • Humans
  • Leukemia, Promyelocytic, Acute / drug therapy*
  • Leukemia, Promyelocytic, Acute / pathology
  • MicroRNAs / genetics*
  • Microarray Analysis
  • Smad4 Protein / genetics*
  • Transforming Growth Factor beta / metabolism*
  • Tretinoin / pharmacology*


  • MIRN146 microRNA, human
  • MicroRNAs
  • Smad4 Protein
  • Transforming Growth Factor beta
  • Tretinoin