RESUMO
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.
Assuntos
Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , Proteínas de Choque Térmico HSP70/metabolismo , Proteínas Mitocondriais/metabolismo , Neoplasias Nasofaríngeas/irrigação sanguínea , Neovascularização Patológica/genética , RNA Longo não Codificante/genética , Transdução de Sinais , Animais , Apoptose , Western Blotting , Carcinoma , Proliferação de Células , Células Cultivadas , Chaperona BiP do Retículo Endoplasmático , Endotélio Vascular/citologia , Endotélio Vascular/metabolismo , Feminino , Citometria de Fluxo , Imunofluorescência , Humanos , Técnicas Imunoenzimáticas , Camundongos , Camundongos Nus , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patologia , Estadiamento de Neoplasias , Prognóstico , Regiões Promotoras Genéticas/genética , RNA Interferente Pequeno/genética , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
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.
Assuntos
Compostos Benzidrílicos/toxicidade , Movimento Celular/fisiologia , Receptores ErbB/biossíntese , Neoplasias Pulmonares/metabolismo , Sistema de Sinalização das MAP Quinases/fisiologia , Metaloproteinases da Matriz/biossíntese , Fenóis/toxicidade , Receptores de Estrogênio/biossíntese , Receptores Acoplados a Proteínas G/biossíntese , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Relação Dose-Resposta a Droga , Estrogênios não Esteroides/toxicidade , Humanos , Neoplasias Pulmonares/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/fisiologiaRESUMO
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.