The ubiquitin-protein ligase E3C (UBE3C) belongs to the E3 ligase enzyme family and implicates in the ubiquitin-proteasome pathway, thus regulates physiological and cancer-related processes. Here, we investigated the expression and roles of UBE3C in glioma. We demonstrated that UBE3C was overexpressed in glioma tissues and cell lines. Inhibition of UBE3C expression in glioma cells significantly decreased cell migration and invasion in vitro. Mechanistically, we disclosed that UBE3C physically interacted with and ubiquitinated tumor suppressor gene annexin A7 (ANXA7), resulting in ubiquitination and degradation of ANXA7. Our results also revealed that increased UBE3C expression was accompanied by a reduction in ANXA7 protein expression in glioma tissues, but not ANXA7 mRNA. Importantly, the inhibition of ANXA7 expression in gliomas cells with UBE3C interference could rescue the cell invasion. Clinically, UBE3C overexpression significantly correlated with high-grade tumors (p < 0.05), poor overall survival, and early tumor recurrence. Thus, our data reveal that high UBE3C expression contributes to glioma progression by ubiquitination and degradation of ANXA7, and thus presents a novel and promising target for glioma therapy.
Background: The stability ratio (SR) is an important biomechanical parameter for evaluating glenoid stability in patients with recurrent anterior shoulder dislocation (RASD), and it cannot be practically and conveniently measured in clinical scenarios. Purpose: To investigate a novel computed tomography (CT)–based protocol to estimate the SR efficiently. Study Design: Descriptive laboratory study. Methods: A total of 102 patients with RASD were included. Demographic information, CT scans, and bone defect area (BDA) were collected. The new protocol, based on balance stability angle (BSA) measurements on CT, was conducted to estimate the SR (SRCT) by 2 surgeons independently. Biomechanical testing was then performed on patient-specific 3-dimensional (3D)–printed glenoid models to calculate the SR (SR3Dprint), which was used to (1) analyze the reliability of SRCT and (2) examine if the BDA could predict SR3Dprint. To validate whether the 3D-printed glenoid could reflect the actual biomechanical properties of the shoulder, the SR from 5 cadaveric glenoid specimens (SRcadaver) was also calculated and compared with that from the 3D-printed glenoid (SR3Dprint) under 6 osteotomy conditions. Linear regression and intraclass correlation coefficients (ICCs) were used for statistical analysis. Results: The interrater reliability of SRCT measurements was high (ICC = 0.95). SRCT was highly correlated with SR3Dprint ( R 2 = 0.86; ICC = 0.92). The mean BDA was 11.44% ± 6.72% by the linear ratio method, with a weak correlation with SR3Dprint ( R 2 = 0.31; ICC = -0.46). The cadaveric validation experiment indicated that SRcadaver was highly correlated with SR3Dprint ( R 2 = 0.86; ICC = 0.77). Conclusion: Results indicated that (1) the proposed CT-based protocol of obtaining BSA measurements is promising for the SR estimation in patients with RASD, (2) the BDA was not an effective parameter to predict the biomechanical SR, and (3) the 3D-printed glenoid could reflect the biomechanical properties of cadaveric shoulders regarding the SR estimation. Clinical Relevance: Traditional BDA measurements cannot accurately reflect the biomechanical stability of the glenoid. The newly proposed CT-based protocol is practical for surgeons to estimate the SR.
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