Epigenetic regulation of microRNA-128a expression contributes to the apoptosis-resistance of human T-cell leukaemia jurkat cells by modulating expression of fas-associated protein with death domain (FADD)

Biochim Biophys Acta. 2014 Mar;1843(3):590-602. doi: 10.1016/j.bbamcr.2013.11.022.


Increased expression of miR-128a is often observed in acute lymphoblastic leukaemia (ALL) compared with its expression in acute myeloid leukaemia (AML). The objective of this study was to investigate the role of miR-128a, especially that in the Fas-signalling pathway, in T-cell leukaemia cells. The role of miR-128a in Fas-mediated apoptosis was examined by using Fas-activating antibody (CH-11)-susceptible Jurkat cells and -resistant Jurkat/R cells. Whereas ectopic expression of miR-128a conferred Fas-resistance on Jurkat cells by directly targeting Fas-associated protein with death domain (FADD), antagonizing miR-128a expression sensitized Jurkat/R cells to the Fas-mediated apoptosis through derepression of FADD expression. Myeloid leukaemia HL60 and K562 cells were also CH-11-resistant, sharing a similar resistant mechanism with Jurkat/R cells. Furthermore, CH-11 induced demethylation of the promoter region of miR-128a with resultant up-regulation of miR-128a expression in Jurkat/R cells, which was shown to be a mechanism for the resistance ofJurkat/R cells to Fas-mediated apoptosis. Our results indicate that the induction of miR-128a expression by DNA demethylation is a novel mechanism of resistance to Fas-mediated apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Cell Line, Tumor
  • DNA Methylation
  • Epigenesis, Genetic
  • Fas-Associated Death Domain Protein / biosynthesis
  • Fas-Associated Death Domain Protein / genetics*
  • Gene Expression
  • HL-60 Cells
  • Humans
  • Jurkat Cells
  • K562 Cells
  • Leukemia, T-Cell / genetics*
  • Leukemia, T-Cell / pathology*
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics*
  • Promoter Regions, Genetic
  • Signal Transduction
  • Up-Regulation
  • fas Receptor / biosynthesis
  • fas Receptor / genetics*


  • FADD protein, human
  • FAS protein, human
  • Fas-Associated Death Domain Protein
  • MIRN128 microRNA, human
  • MicroRNAs
  • fas Receptor