Xu Yang1, Weichun Ni, Ke Lei. 1. Department of Otorhinolaryngology, Shanghai Xuhui Center Hospital, Shanghai, China.
Abstract
BACKGROUND/AIMS: MicroRNAs (miRNAs) are a class of small noncoding RNA molecules that play important roles in carcinogenesis and tumor progression. We investigated the roles and mechanisms of miR-200b in human nasopharyngeal carcinoma (NPC). METHODS: We used quantitative real-time polymerase chain reaction (qRT-PCR) analyses to measure levels of miR-200b and Notch1 in NPC specimens and cell lines. Human NPC cell lines stably expressing miR-200b or control were used to analyze the tumour-suppressive effect of miR-200b. Luciferase reporter assays were used to determine the association between miR-200b and the Notch1 3' untranslated region. RESULTS: We found that miR-200b is significantly downregulated in NPC tissues and cell lines. Gain-of-function and loss-of-function studies demonstrated that miR-200b suppresses NPC cell growth, migration and invasion in vitro. Importantly, overexpression of miR-200b effectively repressed tumor growth in nude mouse models. Integrated analysis identified Notch1 as a direct and functional target of miR-200b. Overexpression of Notch1 reversed the inhibitory effect of miR-200b on NPC cell growth and invasion. CONCLUSION: These results indicate that miR-200b exerts tumor-suppressive effects in NPC carcinogenesis through the suppression of Notch1 expression and suggest a therapeutic application of miR-200b in NPC.
BACKGROUND/AIMS: MicroRNAs (miRNAs) are a class of small noncoding RNA molecules that play important roles in carcinogenesis and tumor progression. We investigated the roles and mechanisms of miR-200b in humannasopharyngeal carcinoma (NPC). METHODS: We used quantitative real-time polymerase chain reaction (qRT-PCR) analyses to measure levels of miR-200b and Notch1 in NPC specimens and cell lines. Human NPC cell lines stably expressing miR-200b or control were used to analyze the tumour-suppressive effect of miR-200b. Luciferase reporter assays were used to determine the association between miR-200b and the Notch1 3' untranslated region. RESULTS: We found that miR-200b is significantly downregulated in NPC tissues and cell lines. Gain-of-function and loss-of-function studies demonstrated that miR-200b suppresses NPC cell growth, migration and invasion in vitro. Importantly, overexpression of miR-200b effectively repressed tumor growth in nude mouse models. Integrated analysis identified Notch1 as a direct and functional target of miR-200b. Overexpression of Notch1 reversed the inhibitory effect of miR-200b on NPC cell growth and invasion. CONCLUSION: These results indicate that miR-200b exerts tumor-suppressive effects in NPC carcinogenesis through the suppression of Notch1 expression and suggest a therapeutic application of miR-200b in NPC.