Survivin, a member of the IAP (inhibitor of apoptosis protein) family, plays important roles in maintaining cellular homoeostasis and regulating cell-cycle progression. This IAP is overexpressed in oesophageal cancer cells, leading to uncontrolled cell growth and resistance to apoptosis. CUG-BP1 (CUG-binding protein 1) is an RNA-binding protein that regulates the stability and translational efficiency of target mRNAs. In the present paper, we report that CUG-BP1 is overexpressed in oesophageal cancer cell lines and human oesophageal cancer specimens. CUG-BP1 associates with the 3′-untranslated region of survivin mRNA, thereby stabilizing the transcript and elevating its expression in oesophageal cancer cells. Our results show that overexpression of CUG-BP1 in oesophageal epithelial cells results in increased survivin mRNA stability and consequently survivin protein expression. Conversely, silencing CUG-BP1 in oesophageal cancer cells destabilizes survivin mRNA, lowering the level of survivin protein. In addition, we have found that altering CUG-BP1 expression modulates susceptibility to chemotherapy-induced apoptosis. Overexpression of CUG-BP1 in oesophageal epithelial cells increases resistance to apoptosis, whereas silencing CUG-BP1 makes oesophageal cancer cells more susceptible to chemotherapy-induced apoptosis. Co-transfection experiments with small interfering RNA directed against survivin suggest that the anti-apoptotic role for CUG-BP1 is not entirely dependent on its effect on survivin expression.
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August 2012
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Research Article|
July 27 2012
The RNA-binding protein CUG-BP1 increases survivin expression in oesophageal cancer cells through enhanced mRNA stability
Elizabeth T. Chang;
Elizabeth T. Chang
*Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, U.S.A.
†Baltimore Veterans Affairs Medical Center, Baltimore, MD 21201, U.S.A.
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James M. Donahue;
James M. Donahue
*Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, U.S.A.
†Baltimore Veterans Affairs Medical Center, Baltimore, MD 21201, U.S.A.
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Lan Xiao;
Lan Xiao
*Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, U.S.A.
†Baltimore Veterans Affairs Medical Center, Baltimore, MD 21201, U.S.A.
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Yuhong Cui;
Yuhong Cui
*Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, U.S.A.
†Baltimore Veterans Affairs Medical Center, Baltimore, MD 21201, U.S.A.
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Jaladanki N. Rao;
Jaladanki N. Rao
*Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, U.S.A.
†Baltimore Veterans Affairs Medical Center, Baltimore, MD 21201, U.S.A.
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Douglas J. Turner;
Douglas J. Turner
*Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, U.S.A.
†Baltimore Veterans Affairs Medical Center, Baltimore, MD 21201, U.S.A.
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William S. Twaddell;
William S. Twaddell
‡Department of Pathology, University of Maryland School of Medicine, Baltimore, MD 21201, U.S.A.
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Jian-Ying Wang;
Jian-Ying Wang
*Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, U.S.A.
†Baltimore Veterans Affairs Medical Center, Baltimore, MD 21201, U.S.A.
‡Department of Pathology, University of Maryland School of Medicine, Baltimore, MD 21201, U.S.A.
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Richard J. Battafarano
Richard J. Battafarano
*Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, U.S.A.
†Baltimore Veterans Affairs Medical Center, Baltimore, MD 21201, U.S.A.
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Biochem J (2012) 446 (1): 113–123.
Article history
Received:
January 16 2012
Revision Received:
May 24 2012
Accepted:
May 30 2012
Accepted Manuscript online:
May 30 2012
Citation
Elizabeth T. Chang, James M. Donahue, Lan Xiao, Yuhong Cui, Jaladanki N. Rao, Douglas J. Turner, William S. Twaddell, Jian-Ying Wang, Richard J. Battafarano; The RNA-binding protein CUG-BP1 increases survivin expression in oesophageal cancer cells through enhanced mRNA stability. Biochem J 15 August 2012; 446 (1): 113–123. doi: https://doi.org/10.1042/BJ20120112
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