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Tristetraprolin down-regulates IL-23 expression in colon cancer cells

  • Research Article
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Molecules and Cells

Abstract

Interleukin 23 (IL-23) is an inflammatory cytokine that plays an important role in tumor promotion. Expression of IL-23 is increased in cancer cells and correlates with tumor progression. However, the mechanisms regulating IL-23 expression in cancer cells are still unclear. Here we report that tristetraprolin (TTP), an AU-rich element (ARE)-binding protein, inhibits IL-23 production in CT26 mouse colon cancer cells. Overexpression of TTP decreased the stability of IL-23 mRNA and the expression level of IL-23 in CT26 cells. Conversely, inhibition of TTP by siRNA increased IL-23 production. TTP destabilized a luciferase mRNA reporter containing the IL-23 mRNA 3’UTR, which contains five AREs. Analyses of deletion and point mutants of the IL-23 mRNA 3’UTR demonstrated that the ARE cluster between the third and fifth AREs was responsible for TTP-mediated destabilization of IL-23 mRNA. A RNA electrophoretic mobility shift assay confirmed that TTP binds to this ARE cluster. Taken together, these results demonstrate that TTP acts as a negative regulator of IL-23 gene expression in mouse colon cancer cells and suggest its potential application as a novel therapeutic target to control IL-23-mediated tumor promotion.

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Authors and Affiliations

  1. Department of Biological Sciences, University of Ulsan, Ulsan, 680-749, Korea

    Hyun Hee Lee, Mai-Tram Vo, Byung Ju Lee & Jeong Woo Park

  2. Department of Biological Sciences, Dong-A University, Busan, 604-714, Korea

    Hyun Hee Lee & Sun-Hee Leem

  3. Department of Surgery, University of Ulsan College of Medicine, Ulsan, 682-060, Korea

    Song Soo Yang

  4. Biomedical Research Center, University of Ulsan College of Medicine, Ulsan, 682-060, Korea

    Wha Ja Cho

  5. Department of Anesthesiology and Pain Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, 682-060, Korea

    Sang-Hyun Lee

  6. Department of Pathology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, 682-060, Korea

    Hee Jeong Cha

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  1. Hyun Hee Lee
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  9. Jeong Woo Park
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Correspondence to Hee Jeong Cha or Jeong Woo Park.

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These authors contributed equally to this work.

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Lee, H.H., Yang, S.S., Vo, MT. et al. Tristetraprolin down-regulates IL-23 expression in colon cancer cells. Mol Cells 36, 571–576 (2013). https://doi.org/10.1007/s10059-013-0268-6

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  • DOI: https://doi.org/10.1007/s10059-013-0268-6

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