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

TL;DR

TRIM47 promotes thyroid cancer by causing ADAR protein degradation through ubiquitination, offering a new treatment target.

Contribution

This study reveals a novel TRIM47-ADAR-GSK-3β axis in thyroid carcinoma progression.

Findings

TRIM47 expression is elevated in thyroid carcinoma tissues and cell lines.

TRIM47 enhances cancer cell malignancy and drug resistance.

TRIM47 interacts with ADAR via ubiquitination, leading to ADAR degradation.

Abstract

Tripartite motif 47 (TRIM47) plays a vital role in the carcinogenesis and drug resistance of various cancers, whereas the function of TRIM47 in thyroid carcinoma (TC) remains unclear.

Human study and animal experiments were performed. Mass spectrometry, cellular invasion/metastasis assay, chemo-resistance assay, and ubiquitination evaluation were conducted to investigate the interaction between TRIM47 and adenosine deaminases acting on RNA (ADAR).

TRIM47 expression was increased in human tissues and cell lines of TC. Functional experiments demonstrated that TRIM47 expression enhanced malignant biological behaviors. With mass spectrometry, TRIM47 silencing could significantly decrease the chemo-resistance of TC cells to chemotherapeutic drugs. The interaction between TRIM47 and ADAR was mediated through the ubiquitin–proteasome pathway (UPP), which was approved by RNA interference procedure and co-immunoprecipitation.

Comprehensively, glycogen synthase kinase-3β (GSK-3β)-associated ubiquitination is critical in the TRIM47-ADAR-GSK-3β axis. This study demonstrates that TRIM47 interacted with ADAR to facilitate ADAR protein degradation via ubiquitination and GSK-3β-associated phosphorylation, which serves as a novel therapeutic avenue for TC.

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