TRIM47是胆囊癌的一种预后生物标志物,通过调节PARP1的K63连接泛素化促进肿瘤进展。

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

作者信息

Xu Ming, Deng Chuanmin, Man Zhongran, Zhu Hongyi

机构信息

Department of Hepatic-Biliary-Pancreatic Surgery, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China.

Department of Hepatic-Biliary-Pancreatic Surgery, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China; Department of Biliary-Pancreatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

出版信息

Transl Oncol. 2025 Jan;51:102164. doi: 10.1016/j.tranon.2024.102164. Epub 2024 Nov 2.

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.

摘要

背景

胆囊癌(GBC)是全球最致命的恶性肿瘤之一,预后极差。先前的研究表明,含三联基序蛋白47(TRIM47)参与多种癌症的进展。然而,TRIM47在GBC中的分子机制和功能仍不清楚。

方法

采用免疫组织化学评估TRIM47的临床意义。在体外和体内进行功能试验,以确定TRIM47在GBC中的作用。进行质谱分析、蛋白质印迹和免疫沉淀试验,以研究其中涉及的分子机制。

结果

在本研究中,TRIM47在GBC组织中上调,与较短的总生存率相关,且TRIM47参与GBC细胞的增殖、迁移和凋亡。机制上,TRIM47与PARP1相互作用,介导PARP1的K63连接的多聚泛素化,从而稳定其表达。此外,TRIM47通过PARP1激活AKT信号通路。

结论

本研究表明,TRIM47促进GBC的进展,因此是预测GBC预后和治疗干预的重要生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec4a/11567951/f7d434ff0111/ga1.jpg

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