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

IF 6.4 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Medicine Pub Date : 2025-07-05 DOI:10.1186/s10020-025-01298-z

Hongzhou Liu, Xiaodong Hu, Tan Li, Yuhan Wang, Xiaomin Fu

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引用次数: 0

Abstract

Background: 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.

Methods: 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).

Results: 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.

Conclusion: 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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三方基序47通过ADAR泛素化促进甲状腺癌的发展。

背景：Tripartite motif 47 （TRIM47）在多种癌症的癌变和耐药过程中起着至关重要的作用，而TRIM47在甲状腺癌（TC）中的功能尚不清楚。方法：进行人体研究和动物实验。采用质谱法、细胞侵袭/转移、耐药及泛素化评价等方法研究TRIM47与作用于RNA的腺苷脱氨酶（ADAR）的相互作用。结果：TRIM47在人体组织和TC细胞系中表达升高。功能实验表明，TRIM47的表达增强了恶性生物学行为。质谱分析显示，TRIM47沉默可显著降低TC细胞对化疗药物的耐药。TRIM47与ADAR的相互作用通过泛素-蛋白酶体途径（UPP）介导，经RNA干扰程序和共免疫沉淀验证。结论：综合而言，糖原合成酶激酶-3β (GSK-3β)相关泛素化在TRIM47-ADAR-GSK-3β轴中起关键作用。本研究表明TRIM47与ADAR相互作用，通过泛素化和gsk -3β相关磷酸化促进ADAR蛋白降解，为TC的治疗提供了新的途径。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Medicine 医学-生化与分子生物学

CiteScore

8.60

自引率

0.00%

发文量

137

审稿时长

1 months

期刊介绍： Molecular Medicine is an open access journal that focuses on publishing recent findings related to disease pathogenesis at the molecular or physiological level. These insights can potentially contribute to the development of specific tools for disease diagnosis, treatment, or prevention. The journal considers manuscripts that present material pertinent to the genetic, molecular, or cellular underpinnings of critical physiological or disease processes. Submissions to Molecular Medicine are expected to elucidate the broader implications of the research findings for human disease and medicine in a manner that is accessible to a wide audience.