TRIM47 promotes head and neck squamous cell carcinoma malignant progression by degrading XAF1 through ubiquitination

Changyun Yu1, Chen Zhang1, Qianqian Zhang1

  • 1Department of Otolaryngology Head and Neck Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.

Iscience
|January 21, 2025
PubMed

Insights

Tripartite motif-containing 47 (TRIM47) promotes head and neck squamous cell carcinoma (HNSCC) progression by degrading XAF1, inhibiting apoptosis and autophagy. TRIM47 suppression halts HNSCC growth, offering a potential therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Tripartite motif-containing 47 (TRIM47) is an E3 ligase implicated in tumor development.
  • TRIM47 is frequently overexpressed in various cancers, suggesting a role in tumorigenesis.

Purpose of the Study:

  • To investigate the role of TRIM47 in head and neck squamous cell carcinoma (HNSCC).
  • To elucidate the molecular mechanisms by which TRIM47 influences HNSCC progression.

Main Methods:

  • Quantitative analysis of TRIM47 expression in HNSCC tissues.
  • Cell proliferation, apoptosis, and autophagy assays in HNSCC cell lines with TRIM47 manipulation.
  • Co-immunoprecipitation and Western blotting to study protein interactions and degradation.
  • In vivo tumor xenograft models in animals.

Main Results:

  • TRIM47 is highly expressed in HNSCC tissues and promotes HNSCC cell proliferation.
  • TRIM47 downregulation inhibits proliferation, induces apoptosis, and promotes autophagy, effects partially reversible by autophagy inhibition.
  • TRIM47 interacts with XIAP-associated factor 1 (XAF1), promoting its ubiquitination and degradation.
  • XAF1 overexpression reverses TRIM47-induced proliferation and autophagy inhibition.
  • TRIM47 knockdown inhibits tumor growth in vivo.

Conclusions:

  • TRIM47 promotes HNSCC progression by mediating the ubiquitination and degradation of XAF1.
  • This interaction suppresses apoptosis and autophagy, contributing to tumor development.
  • TRIM47 represents a potential therapeutic target for HNSCC treatment.

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