RESUMEN
GPX4 has attracted much attention as a key molecule of cell ferroptosis, but its role in cell apoptosis is rarely reported, and its role in apoptosis of thyroid cancer (TC) cell has not been reported. The analysis of TCGA database showed that both GPX4 and FKBP8 were highly expressed in TC tumor tissues; The expression of GPX4 and FKBP8 were positively correlated. The immunohistochemical analysis further confirmed that GPX4 and FKBP8 were highly expressed in TC tumor tissues. In addition, the high expression of GPX4 and FKBP8 were both significantly correlated with the poor prognosis of TC. Silencing GPX4 significantly inhibited the proliferation, induced apoptosis of TC cells, and reduced tumor growth in mice. The co-immunoprecipitation assay revealed a physical interaction between GPX4 and FKBP8 observed in the TC cells. Knockdown of FKBP8 significantly inhibited the proliferation and induced apoptosis of TC cells. Rescue experiments suggested that knockdown of FKBP8 could reverse the strengthens of cell proliferation and apoptosis and the higher expression of FKBP8 and Bcl-2 caused by overexpression of GPX4. Our results suggest that the GPX4/FKBP8/Bcl-2 axis promotes TC development by inhibiting TC cell apoptosis, which provides potential molecular targets for TC therapeutic strategies.
Asunto(s)
Apoptosis , Proliferación Celular , Fosfolípido Hidroperóxido Glutatión Peroxidasa , Proteínas Proto-Oncogénicas c-bcl-2 , Proteínas de Unión a Tacrolimus , Neoplasias de la Tiroides , Humanos , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/metabolismo , Neoplasias de la Tiroides/genética , Proteínas de Unión a Tacrolimus/metabolismo , Proteínas de Unión a Tacrolimus/genética , Ratones , Animales , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Fosfolípido Hidroperóxido Glutatión Peroxidasa/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/genética , Línea Celular Tumoral , Femenino , Masculino , Regulación Neoplásica de la Expresión Génica , Pronóstico , Transducción de SeñalRESUMEN
Acinic cell carcinoma (AciCC) is a low-grade, slow-growing malignant tumor that commonly originates from the parotid gland and occasionally from the minor gland of the oral cavity, but rarely from the nasal cavity. Here, we present a 57-year-old woman who presented with an 8-month history of obstruction and epistaxis of the right nasal cavity. Rhinoscopy revealed a reddish-gray fleshy mass with tiny blood vessels on the surface blocking the right postnaris. Computed tomography showed a 3 × 2 cm2 well-demarcated tumor filling the right nasal common meatus with a clear boundary. There were no signs of local bone erosion in the bony window. Magnetic resonance imaging revealed abnormal signals in the nasal meatus with iso-intensity in the T1W1 sequence with homogeneous enhancement. We diagnosed it as a right nasal hemangioma, and the patient underwent endoscopic resection. However, histopathological evaluation of the surgical specimen confirmed a primary AciCC. The patient refused further radical surgery and instead underwent adjuvant radiotherapy. There was no clinical evidence of recurrence for 2 years, and the patient has returned for follow-up yearly. We discuss the clinical nature of sinonasal AciCC and the treatment of this rare condition.