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The Cross-talk between Tristetraprolin and Cytokines in Cancer

Jian Guo1, Hao Wang1, Shiyi Jiang1

  • 1Department of General Surgery and Translational Medicine Center, Nanjing Medical University Affiliated Wuxi Second Hospital, Wuxi, 214002, China.

Anti-Cancer Agents in Medicinal Chemistry
|March 31, 2017
PubMed

Insights

Tristetraprolin (TTP) negatively regulates inflammatory and oncogenic cytokines by binding to mRNA. This cross-regulation between cytokines and TTP impacts cancer development, highlighting complex networks in tumorigenesis.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cancer Research

Background:

  • Cytokines are key mediators of immune responses, with their expression tightly regulated at transcriptional and post-transcriptional levels.
  • AU-rich elements (AREs) in mRNA are crucial for regulating translation and decay, often interacting with specific binding proteins.
  • Tristetraprolin (TTP) is a primary ARE-binding protein known to negatively control cytokine expression.

Purpose of the Study:

  • To review the regulatory mechanisms of cytokine messenger RNA (mRNA).
  • To elucidate the role of TTP in negatively regulating inflammatory and oncogenic cytokines via ARE binding.
  • To examine the reciprocal regulation between cytokines and TTP in various cancers.

Main Methods:

  • Literature review focusing on cytokine mRNA regulation.
  • Analysis of TTP's interaction with AREs in the 3'-untranslated region (3'UTR) of cytokine mRNAs.
  • Investigation of cytokine-mediated effects on TTP expression and function.

Main Results:

  • TTP binds to AREs in cytokine mRNA, leading to decreased translation and increased decay.
  • Certain cytokines influence TTP expression and activity, creating a feedback loop.
  • The interplay between TTP and cytokines is implicated in the complex regulatory networks governing tumorigenesis.

Conclusions:

  • TTP acts as a critical negative regulator of pro-tumorigenic and inflammatory cytokines.
  • The cross-talk between cytokines and TTP is a significant factor in cancer development and progression.
  • Understanding these intricate regulatory networks is vital for cancer research and therapeutic strategies.
Keywords:
ARECytokineTTPcancercross-regulationpost-transcription.

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