RESUMEN
Ubiquitin specific peptidase 49 (USP49) has been reported as a tumor suppressor in several tumors, but its function and molecular mechanism in non-small cell lung cancer (NSCLC) are still unknown. In this study, USP49 was found downregulated in NSCLC primary tissues and cell lines, and high USP49 predicted a positive index for the overall survival of NSCLC patients. Overexpression of USP49 downregulated the expression levels of Cyclin D1, and upregulated p53 expression. Further flow cytometry analysis showed that overexpressed USP49 induced cell cycle arrest at G0/G1 phase. As a result, overexpression of USP49 significantly inhibited cell growth of NSCLC cells. In mechanism, overexpression of USP49 inhibited PI3K/AKT signaling, but knockdown of USP49 enhanced this signaling. Further studies indicated that USP49 deubiquitinated PTEN and stabilized PTEN protein, which suggested that USP49 inhibited PI3K/AKT signaling by stabilizing PTEN in NSCLC cells. In conclusion, we demonstrated that USP49 was functional in NSCLC cells, and inhibited NSCLC cell growth by suppressing PI3K/AKT signaling, suggesting that USP49 could be as a novel target for NSCLC therapy.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/genética , Fosfatidilinositol 3-Quinasas/genética , Proteínas Proto-Oncogénicas c-akt/genética , Ubiquitina Tiolesterasa/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Puntos de Control del Ciclo Celular/genética , Línea Celular Tumoral , Proliferación Celular , Ciclina D1/genética , Ciclina D1/metabolismo , Células HEK293 , Humanos , Pulmón/metabolismo , Pulmón/patología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Fosfohidrolasa PTEN/genética , Fosfohidrolasa PTEN/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Fase de Descanso del Ciclo Celular , Transducción de Señal , Análisis de Supervivencia , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Ubiquitina Tiolesterasa/antagonistas & inhibidores , Ubiquitina Tiolesterasa/metabolismoRESUMEN
OBJECTIVE: To investigate the relation of Fas and Fas ligand (FasL) protein expression with carcinogenesis and metastasis of cardiac carcinoma. METHODS: Immunohistochemistry was used to detect Fas and FasL protein expression in 64 cardiac carcinoma tissue samples and 20 normal gastric tissue samples. Relation between FasL and Fas expression, age and gender of gastric cancer patients, and pathological subtype and lymph node metastasis of gastric cancer was analyzed. RESULTS: The Fas expression level was significantly higher in normal gastric tissue samples than in cardiac carcinoma tissue samples (85.0% vs. 25.0%, P<0.001), while the FasL expression level was significantly lower in normal gastric tissue samples than in cardiac carcinoma tissue samples (30.0% vs. 81.3%, P<0.001). The Fas expression level was significantly higher in invasive lymph nodes than in non-invasive lymph nodes (82.9% vs. 56.5%, P<0.003) and in well-differentiated gastric carcinoma tissue samples than in poorly-differentiated cardiac carcinoma tissue samples (50.0% vs. 18.0%, P=0.015). The FasL expression level was significantly lower in well-differentiated cardiac carcinoma tissue samples than in poorly- differentiated cardiac carcinoma tissue samples (42.9% vs. 84.0%, P=0.021). The Fas and FasL expression levels (25.0% and 81.3%) were significantly different in cardiac carcinoma tissue samples (P<0.001), but had a non-linear correlation (P=0.575). CONCLUSION: Abnormal Fas and FasL expressions in cardiac carcinoma and lymph node tissues are involved in carcinogenesis and metastasis of gastric cancer.
Asunto(s)
Adenocarcinoma/química , Biomarcadores de Tumor/análisis , Cardias/química , Proteína Ligando Fas/análisis , Ganglios Linfáticos/química , Neoplasias Gástricas/química , Receptor fas/análisis , Adenocarcinoma/secundario , Adulto , Cardias/patología , Estudios de Casos y Controles , Diferenciación Celular , Distribución de Chi-Cuadrado , Femenino , Humanos , Inmunohistoquímica , Ganglios Linfáticos/patología , Metástasis Linfática , Masculino , Persona de Mediana Edad , Dinámicas no Lineales , Neoplasias Gástricas/patología , Adulto JovenRESUMEN
OBJECTIVE: To evaluate the influence of fast-track surgery in perioperative period on the clinical outcomes of patients with esophageal cancer. METHODS: Clinical data of 117 patients with esophageal cancer between January 2011 and June 2011 were retrospectively analyzed. Sixty-three cases (study group) were treated with fast-track surgery and 54 cases(control group) were treated according to routine protocol in the perioperative period. RESULTS: The operative time, time to drainage tube removal, and length of hospital stay were significantly shorter in the study group than those in the control group(all P<0.05). Compared with the control group, the medical cost was lower(P<0.05). The overall postoperative complication rate was 7.9% in the study group and 24.1% in the control group(P<0.05). CONCLUSION: Fast-track surgery in the perioperative period for patients with esophageal cancer can promote bowel function recovery and decrease morbidity.