RESUMO
Small ubiquitin-like modifier (SUMO) proteins regulate many important eukaryotic cellular processes through reversible covalent conjugation to target proteins. In addition to its many well-known biological consequences, like subcellular translocation of protein, subnuclear structure formation, and modulation of transcriptional activity, we show here that SUMO-2 also plays a role in mRNA translation. SUMO-2 promoted formation of the active eukaryotic initiation factor 4F (eIF4F) complex by enhancing interaction between Eukaryotic Initiation Factor 4E (eIF4E) and Eukaryotic Initiation Factor 4G (eIF4G), and induced translation of a subset of proteins, such as cyclinD1 and c-myc, which essential for cell proliferation and apoptosis. As expected, overexpression of SUMO-2 can partially cancel out the disrupting effect of 4EGI-1, a small molecule inhibitor of eIF4E/eIF4G interaction, on formation of the eIF4F complex, translation of the cap-dependent protein, cell proliferation and apoptosis. On the other hand, SUMO-2 knockdown via shRNA partially impaired cap-dependent translation and cell proliferation and promoted apoptosis. These results collectively suggest that SUMO-2 conjugation plays a crucial regulatory role in protein synthesis. Thus, this report might contribute to the basic understanding of mammalian protein translation and sheds some new light on the role of SUMO in this process.
Assuntos
Fator de Iniciação 4E em Eucariotos/metabolismo , Fator de Iniciação Eucariótico 4G/metabolismo , Biossíntese de Proteínas , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/metabolismo , Apoptose/genética , Proliferação de Células , Ciclina D1/genética , Ciclina D1/metabolismo , Regulação da Expressão Gênica , Genes Reporter , Células HCT116 , Humanos , Hidrazonas/farmacologia , Complexos Multiproteicos/metabolismo , Ligação Proteica/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Capuzes de RNA , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/genética , Tiazóis/farmacologiaRESUMO
OBJECTIVE: To retrospectively analyze 95 cases of traumatic carotid cavernous fistula treated by endovascular embolization. METHODS: From January 1994 to December 2008, 95 patients with traumatic carotid cavernous fistula were treated in our hospital. All patients received selective cerebral angiography through femoral artery catheterization. Accordingly, 89 cases were treated by detachable balloon embolization, 5 by platinum microcoils and 1 by covered-stent, respectively. RESULTS: In the study, 61 cases achieved successful balloon embolization at the first time. Fifty-six cases had multiple balloons due to the big fistula. Nine cases received balloon embolization twice. But among the 5 patients treated with platinum microcoils, one developed slight brainstem ischemia. After operation the patient had hemiparesis and swallow difficulty, but gradually recovered 3 months later. No neurological deficits were observed in other cases. All the cases recovered. Eighty-five cases were followed up for 1-15 years and no recurrence was found. CONCLUSIONS: The endovascular embolization for traumatic carotid cavernous fistula is minimally invasive, safe, effective and reliable. The detachable balloon embolization is the first choice in the treatment of TCCF.
Assuntos
Oclusão com Balão/métodos , Fístula Carótido-Cavernosa/terapia , Embolização Terapêutica/métodos , Adolescente , Adulto , Idoso , Fístula Carótido-Cavernosa/diagnóstico , Criança , Emergências , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , StentsRESUMO
Esophageal cancer is characterized by rapid clinical progression and poor prognosis due to adjacent tissue invasion and distant organs metastasis at a very early stage. TM4SF3 (transmembrane 4 superfamily 3), a member of tetraspanin family, has been reported as a metastasis associated gene in many types of tumors. Herein, we described new properties of TM4SF3 in tumor metastasis, which suggested that this gene might be involved in esophageal carcinoma metastasis. Western blotting revealed that TM4SF3 was overexpressed in 57.1% (8/14) of esophageal carcinomas and esophageal carcinoma cell lines with high-invasive potential. Exogenous expression of TM4SF3 in two low-invasive esophageal carcinoma cell lines, KYSE150 and EC9706, significantly promoted cell migration and invasion. Upregulating TM4SF3 expression in EC9706 cells promoted xenograft tumor invading into surrounding tissues, enhanced lung metastasis, and shortened the lifespan of mice (median survival EC9706-TM4SF3 106.5 days versus EC9706-Vector 169.0 days, P < 0.0001) in a spontaneous metastasis model. Further studies demonstrated that ADAM12m was upregulated by TM4SF3 overexpression in vitro and in vivo. Abrogating up-expression of ADAM12m by siRNA significantly suppressed TM4SF3-mediated invasion. Together, these data from our studies indicated that overexpression of TM4SF3 in esophageal cancer conferred advantage to the invasion and metastasis of this destructive disease. Upregulated expression of ADAM12m by TM4SF3 might play a key role in TM4SF3-mediated invasion and metastasis. TM4SF3 and ADAM12m might be potential targets of esophageal carcinoma for anti-metastasis therapy.