Regulation of nasopharyngeal carcinoma cell proliferation by targeting Notch 1 with miR-34 a

INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY(2016)

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摘要
Nasopharyngeal carcinoma (NPC) has the highest incidence rate of head and neck cancer and a strong attack capability. miR-34a, a member of microRNA family, has been shown to participate in the regulation of NPC proliferation through Notch1 signaling pathway. Therefore, the regulation of NPC cell proliferation by targeting Notch1 with miR-34a will be investigated in this study. qRT-PCR was used to detect the expression of miR-34a in NPC. Bioinformatics analysis was used to predict the possible targets of miR-34a which were verified by luciferase assay. Mimics-34a was designed according to miR-34a sequence and transfected into NPC cell line CNE1. Western-Blot analysis was used to detect the expression of Notch1 and flow cytometry was used to detect cell cycle distribution in order to analyze the changes in cell proliferation capability. RT-PCR analysis showed that the expression of miR-34a was significantly decreased in NPC cells compared to that in adjacent tissues (P<0.05). Bioinformatics analysis and luciferase reporter gene assay confirmed that Notch1 is one of miR-34a’s potential targets. Overexpression of miR34a resulted in decrease of the expression levels of Notch1, reduction of the number of cells in s phase (P<0.05), elongation of cell cycle, and decrease of cell proliferation. In conclusion, the expression of miR-34a is down-regulated in NPC, and miR-34a can inhibit the proliferation of NPC cells by targeting and reducing the expression of Notch1.
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关键词
miR-34a, Notch1, nasopharyngeal carcinoma, cell proliferation
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