USP51 (Ubiquitin Specific Peptidase 51)

The knockdown of NEK8 resulted in decreased β-catenin protein levels. Taken together, our study reveals that the USP51-NEK8 axis promotes progression of CRC via the β-catenin pathway and could be a potential target for the treatment of CRC.

This review will examine the mechanistic roles of USPs in pancreatic cancer, as well as the tumor behavior and therapeutic resistance that may result from the dysregulation of these proteins. Ultimately, by presenting an opportunity to develop targeted therapies against specific USPs, we hope to emphasize new therapeutic strategies that could positively impact the lives of patients suffering from this aggressive disease.

Finally, we demonstrated that CDK4/6 kinase activity is important for cell migration as well as stabilizing ZEB1 in the mesenchymal breast cancer cell line MDA-MB-231. These insights could pave the way for developing more targeted and effective therapies targeting at ZEB1 and EMT in advanced cancers.

Importantly, we revealed an alternative intervention for specific pharmacological targeting of USP51 for TNBC cell chemosensitization. In conclusion, these findings collectively indicate that the USP51/GRP78/ABCB1 network is a key contributor to the malignant progression and chemotherapeutic resistance of TNBC cells, underscoring the pivotal role of USP51 as a novel therapeutic target for cancer management.

We found that ribociclib can inhibit cell growth in a dose- and time-dependent manner. We examined the mRNA expression of 4 genes. After ribociclib treatment, the mRNA expression of CDK6 and MYH10 decreased (p < 0.01, p < 0.05). The mRNA expression of CDON increased (p<0.05), but no significant changes were observed in ZEB1 mRNA expression. Furthermore, the qRT‒PCR results for miR-141 showed that the expression of miR-141 increased (p<0.01) after 72 h of treatment with ribociclib.

The Overexpression of USP51 mitigated the downregulation of GPX4 induced by BBM.BBM significantly inhibited tumor xenograft growth in nude mice. This discovery positions BBM as a promising therapeutic candidate for the treatment of esophageal cancer.

For the first time, these above findings manifested that USP21 promoted tumorigenicity and stemness of CRC by deubiquitinating and stabilizing ZEB1. This discovery suggested that USP21/ZEB1 axis may provide novel sights for the treatment of CRC.

Importantly, USP51 plays a crucial role in promoting the HIF1A and SENP1-dependent proliferation, migration, stemness, and chemoresistance under hypoxia in colorectal cancer. Together, our data revealed that USP51 is an oncogene stabilizing the pro-survival protein HIF1A, offering a potential therapeutic target for colorectal cancer.

Together, our results demonstrated that the USP51/PD-L1/ITGB1 network potentially contributes to the malignant progression and therapeutic resistance in NSCLC. This knowledge is beneficial to the future design of advanced cancer therapy.

Our results show that USP51 maintains the stemness of NSCLC cells by deubiquitinating TWIST1. Knocking it down reduces both cell stemness and growth of NSCLC cells.