RESUMEN
In Southeast Asia, the prevalence of nasopharyngeal carcinoma (NPC) is high; however, the molecular mechanism governing the progression of NPC is unclear. The results of the present study revealed upregulation of ring finger protein 219 (RNF219) expression in NPC tissues and cells. Overexpression of RNF219 enhanced NPC cell invasion, migration, and proliferation; whereas knockdown of RNF219 had the opposite effects. Mechanistically, RNF219 activated the nuclear factor kappa B (NF-κB) pathway, mainly reflected by increased p65 nuclear translocation, and increased NF-κB pathway target gene expression. NF-κB pathway inhibition in cells overexpressing RNF219 resulted in reduced invasion, migration, and proliferation, confirming that progression of NPC was promoted by RNF219-mediated NF-κB pathway activation. In addition, the expression of RNF219 correlated positively with the activity of the NF-κB pathway, verifying that RNF219 regulates the activity of the NF-κB pathway in the clinical setting. Our results identified a novel therapeutic target that could promote the development of novel treatments for NPC.
Asunto(s)
FN-kappa B , Neoplasias Nasofaríngeas , Humanos , FN-kappa B/genética , FN-kappa B/metabolismo , Carcinoma Nasofaríngeo/genética , Transducción de Señal , Neoplasias Nasofaríngeas/metabolismo , Regulación hacia Arriba , Línea Celular Tumoral , Proliferación Celular/genéticaRESUMEN
OBJECTIVE: To investigate the possible biological function and mechanism of miR-143 in the metastasis of human nasopharyngeal carcinoma (NPC). METHODS: Using bioinformatics to predict the target gene of miR-143, the 3'UTR and mutant 3'UTR of GLI3 gene was cloned into psiCHECK-2 vector. Dual-luciferase reporter gene assay was employed to examine the repression of the GLI3 gene. miR-143 and GLI3 expression levels in 5-8F cells transfected with miR-143 mimics, inhibitor, or siGLI3 were examined, and the changes in the cell migration ability was assessed by Transwell invasion assay. RESULTS: Bioinformatics prediction indicated the Hh pathway transcription gene GLI3 as a target gene of miR-143, and dual-luciferase reporter assay showed that miR-143 directly combined with the 3'UTR of GLI3. qRT-PCR and Western blotting demonstrated that the expression of miR-143 in 5-8F cells was negatively correlated to GLI3 and suppressed the migration of 5-8F cells. CONCLUSION: MiR-143 can inhibit the invasion of NPC cells by negative regulation of GLI3 gene, which sheds light on the role of miR-143 and Hh pathway in NPC.