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Regulation of XAF1 expression in human colon cancer cell by interferon beta: activation by the transcription

Yunwei Sun1, Liang Qiao, Harry Hua-Xiang Xia

  • 1Division of Gastroenterology, Ruijin Hospital, Department of Medicine, The Shanghai Jiao Tong University, PR China.

Cancer Letters
|November 24, 2007
PubMed

Insights

Interferon beta (IFNbeta) boosts XIAP-associated factor 1 (XAF1) expression in colon cancer cells. This induction is regulated by Signal Transducer and Activator of Transcription 1 (Stat1) binding to a specific DNA element in the XAF1 gene promoter.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Immunology

Background:

  • XIAP-associated factor 1 (XAF1) is a tumor suppressor and interferon-stimulated gene.
  • Interferon beta (IFNbeta) inhibits proliferation and induces apoptosis via the Jak-Stat pathway.
  • Understanding IFNbeta's regulation of XAF1 is crucial for cancer therapy.

Purpose of the Study:

  • To investigate the effect of IFNbeta on XAF1 expression.
  • To elucidate the molecular mechanisms, particularly the role of Signal Transducer and Activator of Transcription 1 (Stat1), in mediating this effect.

Main Methods:

  • Gene expression analysis (RT-PCR, Western blot).
  • XAF1 promoter activity assays (luciferase reporter assay).
  • Electrophoretic mobility shift assay (EMSA) and quantitative chromatin immunoprecipitation (Q-ChIP) to assess transcription factor binding.

Main Results:

  • IFNbeta dose- and time-dependently increased XAF1 promoter activity in DLD1 colon cancer cells.
  • An Interferon Stimulated Response Element (ISRE) within the XAF1 promoter (ISRE-XAF1) was identified as essential for basal and IFNbeta-induced activity.
  • IFNbeta-induced XAF1 expression was dependent on Stat1 binding to ISRE-XAF1, as Stat1 knockdown/inhibition reduced XAF1 induction.

Conclusions:

  • IFNbeta induces XAF1 expression in colon cancer cells.
  • This induction is mediated by the transcription factor Stat1 binding to the ISRE site in the XAF1 promoter.
  • XAF1 acts as an immediate early response gene regulated by Stat1 in response to IFNbeta.

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