RESUMO
Aurora A kinase is a cell cycle regulator that is dysregulated in several different malignancies. Nevertheless, its regulatory mechanisms are still not fully understood. Here, we report that ubiquitin specific peptidase 3 (USP3) promotes proliferation and metastasis of esophageal squamous cell carcinoma (ESCC) cells by mediating deubiquitination of Aurora A. Analysis of human clinical samples indicated that USP3 and Aurora A are highly expressed in ESCC. Cellular experiments confirmed that high expression of USP3 and Aurora A in ESCC cells promoted malignant cell proliferation and invasion. In this mechanism, USP3 leads to suppression of Aurora A ubiquitination, resulting less proteasome degradation. We constructed the deubiquitinated mimetic K143R of Aurora A and found that K143R significantly promoted the proliferation and invasion of ESCC cells and was not regulated by the deubiquitination of USP3. Moreover, Aurora A K143R potentiated the kinase activity of Aurora A in ESCC cells. Thus, our findings demonstrate that the tumorigenic feature of ESCC is in part mediated by USP3-facilitated deubiquitination of Aurora A.
Assuntos
Aurora Quinase A/metabolismo , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , Regulação Neoplásica da Expressão Gênica , Proteases Específicas de Ubiquitina/metabolismo , Carcinogênese/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Humanos , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteólise , UbiquitinaçãoRESUMO
OBJECTIVE: To investigate optimal time for early escharectomy after severe scald in minipigs. METHODS: Minipigs inflicted with 35% TBSA full thickness burn were employed in the study, and they were randomly divided into A (n = 7, with escharectomy at 6PSH), and B (n = 7, with escharectomy at 24 PSH) groups. The hemodynamics indices, hemorrheology, and the serum levels of cytokines in the two groups were determined before burns and at 6, 8, 16, 24 and 72PSH. RESULTS: The hemodynamics indices in A group obviously improved compared with those in B group. The cardiac output (CO, 2.28 +/- 0.03 L/min) and right arterial pressure (RAP, 4.54 +/- 0.04 mmHg) in A group recovered to the pre-injury levels at 48 PSH. There was no difference of the hemorrheology indices between the two groups (P > 0.05). The serum contents of cytokines in A group declined to the pre-injury level on 1 PBW, while those in B group were significantly higher than those before injury and those in A group (P < 0.05 or P > 0.01). CONCLUSION: Escharectomy during 6 PBH might be safe and feasible, thus preventing long-term complications effectively.
