1. Mitochondrial catalase induces cells transformation through nucleolin-dependent Cox-2 mRNA stabilization.
- Author
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Liao X, Huang C, Zhang D, Wang J, Li J, Jin H, and Huang C
- Subjects
- Animals, Catalase metabolism, Cell Line, Cell Transformation, Neoplastic metabolism, Cell Transformation, Neoplastic pathology, Cyclooxygenase 2 metabolism, Epithelial Cells cytology, Epithelial Cells enzymology, Hydrogen Peroxide metabolism, Mice, Mitochondria enzymology, Mitochondria pathology, Mitochondrial Proteins metabolism, Phosphoproteins metabolism, Protein Transport, RNA Stability, RNA, Messenger genetics, RNA, Messenger metabolism, RNA-Binding Proteins metabolism, Signal Transduction, Nucleolin, Catalase genetics, Cell Transformation, Neoplastic genetics, Cyclooxygenase 2 genetics, Gene Expression Regulation, Neoplastic, Mitochondria genetics, Mitochondrial Proteins genetics, Phosphoproteins genetics, RNA-Binding Proteins genetics
- Abstract
It's well documented that over-production of reactive oxygen species (ROS) causes detrimental damages to cells. While a low level of ROS, such as H
2 O2 , functions as signaling transducer and motivates cell proliferation in both cancer and non-transformed stem cells. As a double-edged sword, the direct evidence for demonstrating the function of H2 O2 in the cause of tumor is barely characterized in intact cells. In our current study, we found that targeted expression of mitochondrial catalase (mCAT), but not catalase, could significantly reduce the accumulation of H2 O2 in mouse epithelial JB6 Cl41 cells, consequently led to the cell malignant transformation and anchorage-independent cell growth. Further study revealed that this reduction of H2 O2 resulted in the translocation of nucleolin from the cytoplasm to nuclear, and maintaining the nucleolin nuclear location status, and in turn stabilizing the cox-2 mRNA and consequently leading to a COX-2 protein upregulation, as well as malignant transforming mCAT-overexpressed Cl41 cells. Collectively, our studies here provide direct experimental evidence demonstrating a novel function and molecular mechanisms of mCAT in transforming mouse Cl41 cells, and high significance insight into understanding the beneficial aspect of H2 O2 in circumventing tumor promotion and the theoretical basis for the management of H2 O2 in the clinic implementation as a chemotherapeutic strategy., (Copyright © 2017 Elsevier Inc. All rights reserved.)- Published
- 2017
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