RESUMEN
Clinical studies have reported evidence for the involvement of octamerbinding protein 4 (Oct4) in the tumorigenicity and progression of lung cancer; however, the role of Oct4 in lung cancer cell biology in vitro and its mechanism of action remain to be elucidated. Mortality among lung cancer patients is more frequently due to metastasis rather than their primary tumors. Epithelialmesenchymal transition (EMT) is a prominent biological event for the induction of epithelial cancer metastasis. The aim of the present study was to investigate whether Oct4 had the capacity to induce lung cancer cell metastasis via the promoting the EMT in vitro. Moreover, the effect of Oct4 on the ßcatenin/Ecadherin complex, associated with EMT, was examined using immunofluorescence and immunoprecipitation assays as well as western blot analysis. The results demonstrated that Oct4 enhanced cell invasion and adhesion accompanied by the downregulation of epithelial marker cytokeratin, and upregulation of the mesenchymal markers vimentin and Ncadherin. Furthermore, Oct4 induced EMT of lung cancer cells by promoting ßcatenin/Ecadherin complex degradation and regulating nuclear localization of ßcatenin. In conclusion, the present study indicated that Oct4 affected the cell biology of lung cancer cells in vitro through promoting lung cancer cell metastasis via EMT; in addition, the results suggested that the association and degradation of the ßcatenin/Ecadherin complex was regulated by Oct4 during the process of EMT.
Asunto(s)
Cadherinas/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Factor 3 de Transcripción de Unión a Octámeros/genética , Factor 3 de Transcripción de Unión a Octámeros/metabolismo , beta Catenina/metabolismo , Cadherinas/genética , Línea Celular Tumoral , Transición Epitelial-Mesenquimal/genética , Expresión Génica , Humanos , Unión Proteica , Proteolisis , Interferencia de ARN , ARN Interferente Pequeño/genética , Transfección , beta Catenina/genéticaRESUMEN
Previous studies have identified a variety of microRNAs (miRNAs) that have important roles in cancer progression, particularly in tumor invasion and metastasis. Downregulation of miR145 was reported to occur in various types of human cancer; however, the role of miR145 in lung cancer metastasis and its potential mechanisms of action remain to be elucidated. The present study aimed to investigate the effects of miR145 on metastasis and epithelialmesenchymal transition (EMT) in A549 human lung adenocarcinoma cells. In addition, the underlying mechanisms by which miR145 regulates EMT were examined. The miR145 mimic was transfected into A549 cells; cell invasion and adhesion assays were then performed in order to investigate cell metastasis, and western blot analysis was used to examine the expression of EMT markers. In order to further examine the underlying mechanisms by which miR145 regulates EMT, a luciferase reporter assay was performed to determine whether miR145 targeted Oct4. In addition, the expression of Wnt3a and ßcatenin in A549 cells was measured following transfection with small hairpin RNAOct4. To the best of our knowledge, the results of the present study demonstrated for the first time, that miR145 inhibited lung cancer cell metastasis and EMT via targeting the Oct4 mediated Wnt/ßcatenin signaling pathway.