MiR-145, a new regulator of the DNA fragmentation factor-45 (DFF45)-mediated apoptotic network

Mol Cancer. 2010 Aug 6:9:211. doi: 10.1186/1476-4598-9-211.

Abstract

Background: MicroRNA-145 (miR-145) is considered to play key roles in many cellular processes, such as proliferation, differentiation and apoptosis, by inhibiting target gene expression. DNA Fragmentation Factor-45 (DFF45) has been found to be the substrate of Caspase-3, and the cleavage of DFF45 by caspase-3 during apoptosis releases DFF40 that degrades chromosomal DNA into nucleosomal fragments. There are currently no in-depth studies on the relationship between miR-145 and the DFF45 gene.

Results: In this study, we identified DFF45 as a novel target of miR-145. We demonstrated that miR-145 targets a putative binding site in the coding sequence (CDS) of DFF45, and its abundance is inversely associated with DFF45 expression in colon cancer cells. Using a luciferase reporter system, we found that miR-145 suppresses the expression of the luciferase reporter gene fused to the putative binding site of DFF45. The level of DFF45 protein, but not DFF45 mRNA, was decreased by miR-145, suggesting a mechanism of translational regulation. Furthermore, we demonstrate that this specific silencing of DFF45 by miR-145 accounts, at least in part, for the staurosporine-induced tumor cell apoptosis in vitro.

Conclusions: Our study reveals a previously unrecognized function of miR-145 in DFF45 processing, which may underlie crucial aspects of cancer biology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism
  • Apoptosis Regulatory Proteins / physiology*
  • Apoptosis*
  • Base Sequence
  • Binding Sites
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / physiology*
  • Protein Biosynthesis
  • Sequence Homology, Nucleic Acid

Substances

  • Apoptosis Regulatory Proteins
  • MIRN145 microRNA, human
  • MicroRNAs
  • caspase-activated DNase inhibitor