Cell Death Differ: USP39 and TRIM26 affect the occurrence and development of hepatocellular carcinoma by antagonizing the ubiquitination of ZEB1

Hepatocellular carcinoma (HCC) is a malignant tumor with high morbidity and mortality.
In 2018 alone, there were 841,080 HCC patients out of 18.
1 million cancer cases, and 781,631 out of 9.
6 million cancer deaths.
Postoperative recurrence and metastasis of the disease are a major obstacle to the improvement of the prognosis of HCC patients, and the overall 5-year survival rate of patients is low.

Previous studies have shown that the occurrence and development of HCC is related to the abnormal epithelial-mesenchymal transition (EMT) process, which can induce cell migration and spread tumor cells.
The coordination between the ubiquitination and deubiquitination modification of the ubiquitin-proteasome system (UPS) is an important post-translational regulatory mechanism, which can be responsible for the degradation and renewal of EMT-related proteins.

More and more evidences show that the deubiquitinating enzyme USP39 plays a vital role in the occurrence and development of HCC.
However, the related molecular mechanism is not yet clear.

USP39 is highly expressed in human HCC tissues and is related to the poor prognosis of patients

In this study, the researchers found that USP39 is highly expressed in human HCC tissues and is related to the poor prognosis of patients.
In addition, knocking out USP39 can inhibit the proliferation and metastasis of HCC cells by promoting the degradation of ZEB1.

USP39 and TRIM26 play an antagonistic effect in the body and promote the development of HCC

Interestingly, the immune co-precipitation and fluorescent immunostaining experiments show, USP39 direct interaction with TRIM26.
Further studies have shown that TRIM26 is under-expressed in human HCC tissues and inhibits the proliferation and migration of HCC cells.
In HCC, TRIM26 can promote the degradation of ZEB1 protein through ubiquitination.
Researchers found that USP39 and TRIM26 act in an antagonistic mode rather than a competitive mode, and they affect the occurrence and development of HCC by regulating the stability of ZEB1.

All in all, the results of this study reveal a new mechanism by which USP39 and TRIM26 regulate the level of ZEB1 ubiquitination and affect the proliferation and migration of HCC cells.