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Objective: To study the roles of miR-300 in regulating EMT.Methods: The expression levels of miR-300 were examined in epithelial carcinoma cells that underwent an EMT using quantitative reverse transcription-PCR.The role ofmiR-300 in EMT was investigated by transfection of the miR-300 mimic or inhibitor in natural epithelial-mesenchymal phenotype cell line pairs and in transforming growth factor (TGF) beta-induced EMT cell models.A luciferase reporter assay and a rescue experiment were conducted to confirm the target gene of miR-300.The efficacy of miR-300 against tumor invasion and metastasis was evaluated both in vitro and in vivo.Correlation analysis between miR-300 expression and the expression levels of its target gene, as well as tumor metastasis was performed in specimens from patients with head and neck squamous cell carcinoma (HNSCC).