TRIM47 is a prognostic biomarker for gallbladder cancer and promotes tumor progression through regulating K63-linked ubiquitination of PARP1

IF 5 2区医学 Q2 Medicine Translational Oncology Pub Date : 2024-11-02 DOI:10.1016/j.tranon.2024.102164

Ming Xu , Chuanmin Deng , Zhongran Man , Hongyi Zhu

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Abstract

Background

Gallbladder cancer (GBC) is one of the most lethal malignancies worldwide with an extremely poor prognosis. Previous studies have suggested that tripartite motif containing 47 (TRIM47) is involved in the progression of numerous cancers. However, the molecular mechanism and function of TRIM47 in GBC remain unclear.

Methods

The clinical significance of TRIM47 was evaluated using immunohistochemistry. Functional assays were performed in vitro and in vivo to determine the role of TRIM47 in GBC. Mass spectrometric analysis, western blotting, and immunoprecipitation assays were performed to investigate the molecular mechanisms involved.

Results

In this study, TRIM47 was upregulated in GBC tissues and associated with shorter overall survival rates and TRIM47 was involved in GBC cell proliferation, migration, and apoptosis. Mechanistically, TRIM47 interacts with PARP1 and mediates the K63-linked polyubiquitination of PARP1, thereby stabilizing its expression. Furthermore, TRIM47 activated the AKT signaling pathway via PARP1.

Conclusion

The present study revealed that TRIM47 contributes to the progression of GBC and is therefore an important biomarker for predicting the prognosis of GBC and for therapeutic intervention.

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TRIM47 是胆囊癌的预后生物标志物，通过调节 PARP1 的 K63 链接泛素化促进肿瘤进展。

背景：胆囊癌（GBC）是全球致死率最高的恶性肿瘤之一，预后极差。以往的研究表明，含三方基序 47（TRIM47）参与了多种癌症的进展。然而，TRIM47在GBC中的分子机制和功能仍不清楚：方法：使用免疫组化方法评估 TRIM47 的临床意义。在体外和体内进行了功能测试，以确定 TRIM47 在 GBC 中的作用。为研究其中的分子机制，还进行了质谱分析、Western 印迹和免疫沉淀试验：结果：在这项研究中，TRIM47在GBC组织中上调，并与较短的总生存率相关，TRIM47参与了GBC细胞的增殖、迁移和凋亡。从机理上讲，TRIM47与PARP1相互作用，介导PARP1的K63连接多泛素化，从而稳定其表达。此外，TRIM47还通过PARP1激活了AKT信号通路：本研究发现，TRIM47有助于GBC的进展，因此是预测GBC预后和进行治疗干预的重要生物标志物。

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

Translational Oncology ONCOLOGY-

CiteScore

8.40

自引率

2.00%

发文量

314

审稿时长

54 days

期刊介绍： Translational Oncology publishes the results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of oncology patients. Translational Oncology will publish laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer. Peer reviewed manuscript types include Original Reports, Reviews and Editorials.