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Tripartite motif 47 promotes the development of thyroid carcinoma through ADAR ubiquitination

Hongzhou Liu1, Xiaodong Hu2, Tan Li2

  • 1Department of Endocrinology, First Hospital of Handan City, Handan, 056002, Hebei Province, China.

Molecular Medicine (Cambridge, Mass.)
|July 5, 2025
PubMed
Abstract

Insights

Tripartite motif 47 (TRIM47) promotes thyroid cancer progression and chemoresistance by interacting with adenosine deaminases acting on RNA (ADAR). This interaction involves ubiquitination and GSK-3β phosphorylation, offering a new therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Tripartite motif 47 (TRIM47) is implicated in various cancers, but its role in thyroid carcinoma (TC) is unknown.
  • Understanding TRIM47's function in TC is crucial for developing targeted therapies.

Purpose of the Study:

  • To investigate the role of TRIM47 in thyroid carcinoma (TC).
  • To elucidate the interaction between TRIM47 and adenosine deaminases acting on RNA (ADAR) in TC.

Main Methods:

  • Human and animal studies utilizing mass spectrometry, invasion/metastasis assays, chemo-resistance assays, and ubiquitination evaluation.
  • Investigated the TRIM47-ADAR interaction and its regulation via the ubiquitin-proteasome pathway (UPP).

Main Results:

  • TRIM47 expression is elevated in TC tissues and cell lines, enhancing malignant behaviors.
  • TRIM47 silencing reduced chemoresistance in TC cells.
  • TRIM47 interacts with ADAR, leading to ADAR protein degradation through ubiquitination and GSK-3β-associated phosphorylation.

Conclusions:

  • The TRIM47-ADAR-GSK-3β axis is critical in TC pathogenesis.
  • TRIM47 facilitates ADAR degradation via ubiquitination and GSK-3β phosphorylation.
  • This axis presents a novel therapeutic strategy for thyroid carcinoma.
Keywords:
Adenosine deaminases acting on RNAGlycogen synthase kinase-3βPhosphorylationThyroid carcinomaTripartite motif 47Ubiquitination

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