USP46 (Ubiquitin Specific Peptidase 46)

USP46 interacts with and stabilizes BECN1, promoting autophagy and thereby suppressing prostate cancer cell proliferation. In conclusion, the current findings demonstrate that USP46 abolishes cell survival of prostate cancer via enhancing BECN1-dependent autophagy.

These findings collectively suggest that the up-regulated USP46 promotes apoptosis in lung cancer cells through the regulation of TRAF6. Therefore, targeting the USP46/TRAF6 signaling pathway presents a promising therapeutic strategy for lung cancer treatment, potentially offering new avenues for intervention in cancer progression and cell survival mechanisms.

Mechanistically, CK1δ directly phosphorylates USP46 and activates its deubiquitinase activity towards NRAS mutants, thus promoting oncogenic NRAS-driven melanocyte malignant transformation and melanoma progression in vitro and in vivo. Our findings underscore the significance of the CK1δ-USP46 axis in stabilizing oncogenic NRAS mutants and provide preclinical evidence that targeting this axis holds promise as a therapeutic strategy for human melanoma harboring NRAS mutations.

Specifically, in the last few years, the carcinogenic properties of USP46 have become more apparent. In the current review, we provide a comprehensive overview of the current knowledge about USP46 including its characteristics, structure, inhibitors, function in diseases, especially in the nervous system, and the correlation of USP46 with cancers.

Further analysis revealed that bcUSP46 stabilized bcTBK1 by eliminating the K48-linked ubiquitination of bcTBK1. Overall, our findings highlight the unique role of USP46 in modulating TBK1/IFN signaling and enrich our knowledge of the function of deubiquitination in regulating innate immunity in vertebrates.

In conclusion, this study highlights the critical role of the USP46/PTBP1/PKM2 axis in TAM resistance in BC. Targeted therapy against USP46 may represent a promising strategy to improve the prognosis of TAM-resistant patients.

Consequently, Wingless-dependent developmental patterning and tissue homeostasis are disrupted. These results reveal an evolutionarily conserved mechanism that mediates Wnt/Wingless receptor stabilization and underlies the precise activation of signaling throughout the spatial range of the morphogen gradient.

CD9, CD63, and CD81 mRNA levels were high in RB tumors versus control retina, with increased and variable CD9 immunoreactivity in the invasive areas of the tumor. Serum sEVs could serve as a potential liquid biopsy source for understanding TR mechanisms in RB.

2) function of PHLPPs regulatory factor USP46 and miR-190/miR-215, 3) the potential roles of PHLPPs in disease prognosis, Epidermal growth factor receptors (EGFR)- tyrosine kinase inhibitor (TKI) resistance and DNA damage, 4) and the possible function of PHLPPs in radiotherapy, ferroptosis and inflammation response. Therefore, PHLPPs can be considered as either biomarker or prognostic marker for lung cancer treatment.

Importantly, USP46 stimulated the glycolysis and promoted the malignant growth of TNBC cells through upregulation of PGAM1. Our study reveals that USP46/PGAM1 axis contributes to TNBC progression and is a potential target for the treatment of TNBC patients.

Above results suggest that the abnormally over-expressed miR-27a-3p in liver promotes the proliferation of cancer cells and accelerates the development of HCC by targeting inhibition the expression of USP46. Targeting miR-27a-3p may be an effective strategy for prevention and treatment of HCC.

BH4 also increases MM bortezomib (Bor) resistance in vitro and in vivo...Our results demonstrate the important role of BH4 in MM Bor resistance and tumor progression in vivo. These findings could potentially have clinical implications.