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

TRIM47 是胆囊癌的预后生物标志物,通过调节 K63 连接的 PARP1 泛素化来促进肿瘤进展

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作者:Ming Xu, Chuanmin Deng, Zhongran Man, Hongyi Zhu

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.

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.

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.

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