RESUMEN
Nasopharyngeal carcinoma (NPC), as a unique head and neck cancer type, is particularly prevalent in certain geographic areas such as eastern Asia. Until now, the therapeutic options have been restricted mainly to radiotherapy or chemotherapy. However, the clinical treatment effect remains unsatisfactory even if the combined radio-chemotherapies. Therefore, it is urgently needed to develop effective novel therapies against NPC. In this study, we discovered that lncRNA Hotair was extremely abundant in NPC cells and clinical NPC samples. Further studies showed that Hotair knockdown significantly attenuated both in vitro and in vivo tumor cell growth and angiogenesis. Our study also demonstrated that Hotair promoted angiogenesis through directly activating the transcription of angiogenic factor VEGFA as well as through GRP78-mediated upregulation of VEGFA and Ang2 expression. Therefore, Hotair may serve as a promising diagnostic marker and therapeutic target for NPC patients.
Asunto(s)
Biomarcadores de Tumor/genética , Regulación Neoplásica de la Expresión Génica , Proteínas HSP70 de Choque Térmico/metabolismo , Proteínas Mitocondriales/metabolismo , Neoplasias Nasofaríngeas/irrigación sanguínea , Neovascularización Patológica/genética , ARN Largo no Codificante/genética , Transducción de Señal , Animales , Apoptosis , Western Blotting , Carcinoma , Proliferación Celular , Células Cultivadas , Chaperón BiP del Retículo Endoplásmico , Endotelio Vascular/citología , Endotelio Vascular/metabolismo , Femenino , Citometría de Flujo , Técnica del Anticuerpo Fluorescente , Humanos , Técnicas para Inmunoenzimas , Ratones , Ratones Desnudos , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patología , Estadificación de Neoplasias , Pronóstico , Regiones Promotoras Genéticas/genética , ARN Interferente Pequeño/genética , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Lung cancer is one of the leading causes of cancer deaths worldwide. Recent evidences indicated that bisphenol A (BPA), a wide contaminant with endocrine disrupting activity, could enhance the susceptibility of carcinogenesis. Although there are increasing opportunities for lung cells exposure to BPA via inhalation, there is no study concerning the effects of BPA on the development of lung cancer. The present study revealed that BPA less than 10(-4)M had limited effects on the proliferation of lung cancer A549 cells, however, BPA treatment significantly stimulated the in vitro migration and invasion of cells combing with the morphological changes and up regulation of matrix metalloproteinase-2 (MMP-2) and MMP-9. G-protein-coupled estrogen receptor (GPER), while not estrogen receptor α/ß (ERα/ß), mediated the BPA induced up regulation of MMPs. Further, BPA treatment induced rapid activation of ERK1/2 via GPER/EGFR. GPER/ERFR/ERK1/2 mediated the BPA induced upregulation of MMPs and in vitro migration of lung cancer A549 cells. In summary, our data presented here revealed for the first time that BPA can promote the in vitro migration and invasion of lung cancer cells via upregulation of MMPs and GPER/EGFR/ERK1/2 signals, which mediated these effects. This study suggested that more attention should be paid on the BPA and other possible environmental estrogens induced development of lung cancer.
Asunto(s)
Compuestos de Bencidrilo/toxicidad , Movimiento Celular/fisiología , Receptores ErbB/biosíntesis , Neoplasias Pulmonares/metabolismo , Sistema de Señalización de MAP Quinasas/fisiología , Metaloproteinasas de la Matriz/biosíntesis , Fenoles/toxicidad , Receptores de Estrógenos/biosíntesis , Receptores Acoplados a Proteínas G/biosíntesis , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Relación Dosis-Respuesta a Droga , Estrógenos no Esteroides/toxicidad , Humanos , Neoplasias Pulmonares/patología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Regulación hacia Arriba/efectos de los fármacos , Regulación hacia Arriba/fisiologíaRESUMEN
We present a case of right lateral auricle contracture malformation, auricular canal atresia, and complete facial paralysis (House-Brackmann grade VI) caused by a megatemperature hydro-aluminum injury at work. The diastrophic auricle and auricular canal atresia were reshaped. The complete facial paralysis was reanimated to House-Brackmann grade III after surgical hypoglossal-facial end-to-end anastomosis. These outcomes indicate that hypoglossal-facial end-to-end anastomosis is an effective surgical option for successful reanimation of complete facial paralysis.