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/metabolismoAsunto(s)
Aminoácidos/uso terapéutico , Trastornos de la Coagulación Sanguínea/tratamiento farmacológico , Hemorragia/tratamiento farmacológico , Vitamina B 6/uso terapéutico , Heridas y Lesiones/tratamiento farmacológico , Adulto , Anciano , Trastornos de la Coagulación Sanguínea/complicaciones , Combinación de Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Vitamina B 6/administración & dosificación , Heridas y Lesiones/complicaciones , Adulto JovenRESUMEN
OBJECTIVE: To investigate the characteristics of the confined space accident and its medical rescue strategy. METHODS: Thirty-six patients with emergency rescue in the five confined space accident during June 2009 to July 2012 were retrospectively analyzed. RESULTS: Twenty-nine people were caught in four confined space accidents caused by building collapse and 7 people were caught in one confined space accident caused by a tower of babel blast furnace damage which caused severe gas and hydrogen sulfide poisoning. For the 36 wounded, the shortest rescue time was 1.5 hours and the longest was 10.5 hours. Fourteen people were killed (mortality rate 38.89%). Characteristics of the confined space accident: the wounded activity environment was very harsh, the wounded were restricted particularly, the wounded injuries were diverse, the psychological depression was very common. The confined space environment and the complexity of wounded disease determined its medical rescue specificity and were very different from the usual trauma emergency. CONCLUSIONS: Confined space accident caused very painful casualties. The key reason is that the relevant personnel failed to clearly recognize the potential risks in the confined space or nearby, making the confined space into another "quiet killer". This problem needs to be paid highly attention.