Recent studies have indicated that the expression of ubiquitin-specific protease 51 (USP51), a novel deubiquitinating enzyme (DUB) that mediates protein degradation as part of the ubiquitin‒proteasome system (UPS), is associated with tumor progression and therapeutic resistance in multiple malignancies. However, the underlying mechanisms and signaling networks involved in USP51-mediated regulation of malignant phenotypes remain largely unknown. The present study provides evidence of USP51's functions as the prominent DUB in chemoresistant triple-negative breast cancer (TNBC) cells. At the molecular level, ectopic expression of USP51 stabilized the 78 kDa Glucose-Regulated Protein (GRP78) protein through deubiquitination, thereby increasing its expression and localization on the cell surface. Furthermore, the upregulation of cell surface GRP78 increased the activity of ATP binding cassette subfamily B member 1 (ABCB1), the main efflux pump of doxorubicin (DOX), ultimately decreasing its accumulation in TNBC cells and promoting the development of drug resistance both in vitro and in vivo. Clinically, we found significant correlations among USP51, GRP78, and ABCB1 expression in TNBC patients with chemoresistance. Elevated USP51, GRP78, and ABCB1 levels were also strongly associated with a poor patient prognosis. 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.

OBJECTIVE: To explore the change and impact factors of craving for heroin in patients after 6 month methadone maintenance treatment (MMT). METHODS: The questionnaire of craving for heroin was used to measure the level of craving for heroin when patients just entered the study and were treated for 6 months. The influence of MMT on craving in patients were analyzed. RESULTS: The total score and score for other factors decreased except the factor "self-control" after MMT. The craving for high dose patients decreased significantly after 6 month treatment (P<0.05). The degree of craving for heroin in males and females all decreased after MMT, but no significant difference was shown (P>0.05). The craving degree for heroin in patients with long drug use was higher than that of patients with short drug use. After the treatment, the improvement of craving was more significant for the long drug users. CONCLUSION MMT can decline the craving for heroin in drug users. Dosage for methadone and gender may be the risk factors of craving change.
Adult ; China ; Female ; Heroin Dependence ; drug therapy ; psychology ; rehabilitation ; Humans ; Male ; Methadone ; therapeutic use ; Substance Withdrawal Syndrome ; drug therapy ; psychology ; Surveys and Questionnaires ; Young Adult