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

Jianjun Zhang13, Haiyan Guo2*, Guanxiang Qian1, Shengfang Ge1, Huifeng Ji2, Xiaobo Hu2 and Wantao Chen3

Author Affiliations

1 Department of Biochemistry and Molecular Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China

2 Department of Clinical Laboratory, NO.3 people's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China

3 Department of Oral and Maxillofacial Surgery, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai, PR China

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Molecular Cancer 2010, 9:211  doi:10.1186/1476-4598-9-211

Published: 6 August 2010

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.