RESUMO
Recent studies suggested that microRNA-200 family microRNAs play critical roles in cancer initiation and metastasis. The underlying mechanism remained elusive. In this study, we show that microRNA-200c is upregulated in nasopharyngeal carcinoma cells. Manipulation of microRNA-200c levels affected cell growth, migration, and invasion in nasopharyngeal carcinoma cell lines. Furthermore, PTEN was identified as a direct target of microRNA-200c. Overexpression of PTEN resulted in similar effects to those of anti-microRNA-200c transfection. In vivo suppression of microRNA-200c level reduced tumor growth in mice. Overall, our data suggest that microRNA-200c plays an oncogenic role in nasopharyngeal carcinoma by targeting PTEN.
Assuntos
Carcinoma/genética , Transição Epitelial-Mesenquimal/genética , MicroRNAs/genética , Neoplasias Nasofaríngeas/genética , PTEN Fosfo-Hidrolase/genética , Animais , Carcinoma/patologia , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Camundongos , MicroRNAs/antagonistas & inibidores , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/patologia , Invasividade Neoplásica/genética , PTEN Fosfo-Hidrolase/biossíntese , Transfecção , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Hepatocyte growth factor (HGF) was identified as an endogenous tissue protective agent against apoptosis in many cell types. The mechanism by which HGF protects primary endothelial cells (ECs) has not yet been completely elucidated. FOXO1 and FOXO3a, two members of the FOXO family, are the most abundant FOXO isoforms in mature endothelial cells. In this study, we aimed to explore whether FOXO1 and FOXO3a play similar roles in HGF-mediated protection against apoptosis in mature endothelial cells. Our result showed that HGF prevented ECs from oxidative-stress induced apoptosis in part by inducing the phosphorylation of FOXO proteins. FOXO1 and FOXO3a are equally important in this process by regulating the expression of Bim, PUMA, FasL, and TRAIL.
