Deubiquitinating enzyme USP10 promotes osteosarcoma metastasis and epithelial-mesenchymal transition by stabilizing YAP1.

BACKGROUND: Osteosarcoma (OS) is a fatal adolescent tumor, which is susceptible to remote metastases at an early stage, and its treatment remains a major challenge. ubiquitin-specific protease 10 (USP10) is primarily located in the cytoplasm and can therefore deubiquitinate various cytoplasmic proteins. However, the expression and mechanism of USP10 in OS remain ambiguous. The aim of this study was to explore how USP10 affects Yes-associated protein1 (YAP1) to influence the metastasis and epithelial-mesenchymal transition (EMT). METHODS: Western blotting, qRT-PCR, and immunohistochemical (IHC) analyses were performed to evaluate USP10 and YAP1 levels. Using wound healing and transwell tests, the roles and molecular pathways of USP10 and YAP1 ability to migrate and invade of OS were investigated, and cell morphological alterations were examined using phalloidin staining. RESULTS: Our results indicated that USP10, a new type of deubiquitinating protease, is increased in OS tissues and cells contrasted with adjacent healthy tissues. Overexpression of USP10 correlated with tumor size, distant metastasis, and TNM stage, and was an independent factor of poor prognosis in OS patients. Also, USP10 expression is closely connected with the incident of OS metastasis and tumor size. Functional assays revealed that USP10 knockdown suppressed cell migrating and invading ability and inhibited the EMT of OS cells in vivo and in vitro. In addition, we showed that USP10 knockdown decreased the levels of YAP1, which is an important positive regulator of migration and invasion in many cancers. We also found a significant positive correlation between USP10 and YAP1 levels, further demonstrating that USP10-induced migration and EMT are based on YAP1 in OS cells. In a mechanistic way, USP10 stabilizes the expression of YAP1 by mediating its deubiquitination in OS cells. CONCLUSION: Together, this study showed that USP10 can directly interact with YAP1 to reduce ubiquitinated YAP1, thereby stabilizing its protein levels and affecting EMT and distant metastasis in OS cells.

Vacuum sealing drainage system combined with an antibacterial jackfruit aerogel wound dressing and 3D printed fixation device for infections of skin soft tissue injuries.

Injuries and infections of skin and soft tissue are commonly encountered in primary health care and are challenging to manage. Vacuum sealing drainage (VSD) is generally used in clinical treatment, but current commercial methods of VSD have some disadvantages, such as easy blockage, nonantibacterial effects, and inconvenient curved surfaces. Herein, we report a functional zinc oxide/jackfruit aerogel (ZnO/JFA) composite material that is ultralight, superabsorbent and antibacterial as a new antibacterial VSD wound dressing. The JFA is carbonized from fresh jackfruit, and the JFA exhibits superhydrophilicity and superabsorbability. The water absorption rate of JFA was up to 1209.39%, and the SBF absorption rate was up to 1384.22%. The water absorption rate of ZnO/JFA was up to 494.47%, and the SBF absorption rate was up to 473.71%. The JFA and ZnO/JFA possess a pipeline structure, which is beneficial for absorbing wound exudates. In addition, surface modification of nanosized ZnO and its effects on antibacterial properties and biocompatibility were performed. When the concentration of ZnO/JFA was 3.125 mg/mL, the survival rate of human fibroblast cells was close to 80%, while the antibacterial rates against Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli were up to 99.06%, 75.28% and 93.58%, respectively. Moreover, a 3D printed assisted device was introduced to make the ZnO/JFA wound dressing more attached to the bottom of the wound on a curved surface. An integrated device was formed under the printing mold, and then animal experiments were conducted in vivo. The results showed that a healing rate of almost 100% for infected skin wounds was obtained with this novel VSD device after 14 days, compared to only 79.65% without the VSD device. This novel VSD with a negative pressure suction dressing is beneficial for healing infectious wounds.