MiR-145, a new regulator of the DNA fragmentation factor-45 (DFF45)-mediated apoptotic network.
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.
Zhang
Jianjun
J
Department of Biochemistry and Molecular Biology, Shanghai Jiao TongUniversity School of Medicine, Shanghai, PR China.
Guo
Haiyan
H
Qian
Guanxiang
G
Ge
Shengfang
S
Ji
Huifeng
H
Hu
Xiaobo
X
Chen
Wantao
W
D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D001483:Base Sequence; D001665:Binding Sites; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D014176:Protein Biosynthesis; D012689:Sequence Homology, Nucleic Acid
D051017:Apoptosis Regulatory Proteins; C541010:MIRN145 microRNA, human; D035683:MicroRNAs; C109664:caspase-activated DNase inhibitor