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Tristetraprolin regulates phagocytosis through interaction with CD47 in head and neck cancer

Won Hyeok Lee1, Song Hee Kim1, Jae Hee An1

  • 1Department of Otolaryngology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan 44033, Republic of Korea.

Experimental and Therapeutic Medicine
|August 18, 2022
PubMed

Insights

Decreased Tristetraprolin (TTP) causes CD47 overexpression in radioresistant head and neck cancer. TTP enhances phagocytosis by degrading CD47 mRNA, offering a potential biomarker for cancer therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • CD47, a protein overexpressed in head and neck cancer, inhibits macrophage phagocytosis.
  • The mechanisms driving CD47 overexpression in radioresistant head and neck cancer remain unclear.

Purpose of the Study:

  • To investigate the role of Tristetraprolin (TTP) in CD47 overexpression in radioresistant head and neck cancer.
  • To elucidate the regulatory mechanism of CD47 expression by TTP.
  • To explore the potential of TTP as a biomarker for CD47-positive head and neck cancer.

Main Methods:

  • Reverse transcription-quantitative PCR and Western blotting to assess gene and protein expression.
  • Phagocytosis assays to evaluate the impact of CD47 on immune cell activity.
  • TTP transfection, RNA interference, dual-luciferase assays, and electrophoretic mobility shift assays (EMSA) to study molecular interactions.
  • Methylation-specific PCR to investigate epigenetic modifications.

Main Results:

  • Decreased Tristetraprolin (TTP) expression was correlated with sustained CD47 overexpression in radioresistant head and neck cancer cells (HN31R).
  • CD47 overexpression was shown to inhibit macrophage phagocytosis.
  • TTP transfection enhanced phagocytosis by directly binding to CD47 mRNA's 3' untranslated region (3'UTR) and promoting its degradation.
  • DNA methyltransferase 1 (DNMT1) was overexpressed in radioresistant HN31R cells, leading to epigenetic silencing of TTP via DNA methylation.

Conclusions:

  • Tristetraprolin (TTP) plays a critical role in regulating CD47 expression in radioresistant head and neck cancer.
  • TTP enhances anti-tumor immunity by degrading CD47 mRNA, thereby promoting phagocytosis.
  • Epigenetic silencing of TTP by DNMT1 contributes to CD47 overexpression and immune evasion.
  • TTP emerges as a promising biomarker for CD47-positive head and neck cancer patients, potentially guiding therapeutic strategies.
Keywords:
AU-rich elementsCD47DNA methyltransferasehead and neck cancerphagocytosispost-transcriptional modificationradioresistancetristetraprolin

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