USP13 (Ubiquitin Specific Peptidase 13)

A USP13 inhibitor, 2-Methoxyestradiol (2-Met), was used to evaluate its therapeutic efficacy...Pharmacological inhibition or knockdown of USP13 impedes HCC progression, induces ferroptosis, and enhances T cell-mediated cytotoxic effects. These results highlight that USP13 could be a promising therapeutic target for HCC.

Suggested by the DRESIS Database, NF-κB and Notch signaling cascades are key to the resistance of Doxorubicin (Dox) and cyclophosphamide (CTX) within the standard R-CHOP regimen of DLBCL hinting benefits of combining Spautin-1 with Dox or CTX. Altogether, these results demonstrate USP13 deubiquitinates Ran in DLBCL, and Spautin-1 well synergizes with Dox or CTX to initiate ferroptosis. Combinational treatment with Spautin-1 and Dox or CTX may represent an effective approach and therapeutic hope to combat with DLBCL.

Clinical correlation analysis of CRC patient specimens revealed a strong positive correlation between USP13 and MKK3 expression levels, with elevated USP13 expression associated with advanced disease stage. Our findings not only establish the USP13-MKK3-p38 axis as a crucial molecular pathway in CRC progression but also identify USP13 as a promising therapeutic target.

Taken together, our current findings suggest that the METTL3-mediated m6A modification of circCDYL promotes the progression of gastric cancer via the miR-378a-5p/USP13 axis. CircCDYL is expected to be a potential diagnostic biomarker and therapeutic target for gastric cancer.

In vivo experiments revealed that USP13 knockdown suppressed CC tumor growth by modulating ECT2 expression. Together, USP13 exacerbates the malignant progression of CC by inhibiting ECT2 ubiquitination, suggesting that targeting the USP13-ECT2 axis might be a potential therapeutic strategy for CC with notable clinical significance.

The loss of USP13 significantly potentiates TNF-α/SMAC mimetic birinapant/pan-caspase inhibitor Z-VAD-FMK (TBZ)-induced necroptosis in CRC cells and diminishes tumor growth in a xenograft model. Thereby, USP13 may serve as a potential therapeutic target for anticancer treatment of CRC.

In vivo, Deme significantly suppressed tumor growth without apparent toxicity to vital organs. Together, these data suggest that Deme is a promising and safe anti-tumor compound that downregulates HK2 expression, providing a potential therapeutic strategy for OSCC treatment.

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.

Moreover, high USP13 expression in DLBCL is associated with poor prognosis and blocks CD8+ T cell infiltration. In summary, Spautin-1 may inhibit the growth of DLBCL cells by promoting mitochondrial damage-mediated PANoptosis and anti-tumor immunity, providing a potential strategy for DLBCL therapy.

USP10's therapeutic significance drives inhibitor development (Spautin-1, D1, Wu-5, P22077, Parthenolide), though cross-reactivity within the USP family due to conserved catalytic domains remains a challenge. Novel strategies like PROTACs and engineered ubiquitin variants (UbVs) offer promise for future selective targeting of USP10 dysregulation in diverse diseases. A comprehensive understanding of its structure and context-specific functions is essential for exploiting its full therapeutic potential.

The results of immunohistochemical staining of tumor tissue also indicated that the expression level of USP13 was negatively related to the prognosis of DLBCL patients. These new findings provided an experimental basis for overcoming Ibrutinib resistance in DLBCL and showed that USP13 is a potential therapeutic target and prognostic marker in DLBCL.