RESUMEN
The roles of gap junctions (GJs) and its components, connexins, in the autophagy of cervical cancer cells have been rarely investigated. Our previous study demonstrated that connexin 32 (Cx32) exerted an antiapoptotic effect on cervical cancer. However, as an important regulator of apoptosis, whether the autophagy is involved in the function of Cx32 on cervical cancer cells is not well defined. The present study aimed to investigate the role of Cx32 on autophagy and apoptosis inhibition in cervical cancer cells. The expression levels of Cx32 and the autophagyassociated protein LC3â ¡ in paracancerous cervical tissues (n=30) and cervical cancer (n=50) tissues were determined via western blotting. In total, 45 cervical cancer specimens were used to evaluate the clinical relevance of Cx32 and LC3â ¡. It was found that both Cx32 and LC3â ¡ were upregulated in cervical cancer tissues compared with those in paracancerous cervical tissues. The effect of Cx32 on autophagy was examined by detecting the change of LC3â ¡ using western blotting, transfection with enhanced green fluorescent proteinLC3 plasmid and transmission electron microscopy analysis. Overexpression of Cx32 significantly enhanced autophagy in HeLaCx32 cells, whereas knockdown of Cx32 suppressed autophagy in C33A cells. The flow cytometry results demonstrated that Cx32 inhibited the apoptosis of cervical cancer cells by promoting autophagy. Moreover, Cx32 triggered autophagy via the activation of the AMPactivated protein kinase (AMPK) signalling, regardless of the presence or absence of GJs. Collectively, it was identified that Cx32 exerted its antiapoptotic effect by activating autophagy via the AMPK pathway in cervical cancer, which demonstrates a novel mechanism for Cx32 in human cervical cancer progression.
Asunto(s)
Proteínas Quinasas Activadas por AMP/metabolismo , Autofagia/genética , Conexinas/farmacología , Neoplasias del Cuello Uterino/genética , Autofagia/fisiología , Línea Celular Tumoral/metabolismo , Conexinas/metabolismo , Femenino , Humanos , Transducción de Señal/genética , Neoplasias del Cuello Uterino/fisiopatología , Proteína beta1 de Unión ComunicanteRESUMEN
Yeshes Palbyor was born in Haiyan County, Qinghai Province in 1704. As a youngster he studied medicine, Buddhism and linguistics in Ta'er Monastery. At the age of 28, he returned to Gunglung Monastery in his home town until his death. He devoted his whole life to the study of clinical therapeutics and Mongolian medicine. Gan lu si bu was his representative work, in which he advanced the theory of Six Basic Syndromes and Chills and Fever.