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Feedback loop in miR‐449b‐3p/ADAM17/NF‐κB promotes metastasis in nasopharyngeal carcinoma

An emerging body of evidence has promoted the understanding of the role of microRNAs (miRNAs) in tumorigenesis and progression, but the mediating function of miRNAs in nasopharyngeal carcinoma (NPC) development remains poorly elucidated. In this study, miR‐449b‐3p was downregulated in NPC specimens...

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Detalles Bibliográficos
Autores principales: Fei, Qian, Du, Ming‐Yu, Qian, Lu‐Xi, Chen, Han‐Bo, Chen, Jie, Zhu, Hong‐Ming, Tian, Xiao‐Kang, Jiang, Ning, Gu, Jia‐Jia, He, Xia, Yin, Li
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6792493/
https://www.ncbi.nlm.nih.gov/pubmed/31433128
http://dx.doi.org/10.1002/cam4.2469
Descripción
Sumario:An emerging body of evidence has promoted the understanding of the role of microRNAs (miRNAs) in tumorigenesis and progression, but the mediating function of miRNAs in nasopharyngeal carcinoma (NPC) development remains poorly elucidated. In this study, miR‐449b‐3p was downregulated in NPC specimens (P < .001) and cells (P < .05). Cytological and animal experiments provided evidence that miR‐449b‐3p inhibited NPC metastasis in vitro and in vivo. Disintegrin and metalloproteinase 17 (ADAM17) was revealed as a direct target of miR‐449b‐3p. Rescue experiments suggested that the downregulation of ADAM17 in the miR‐449b‐3p knockdown cells partially reversed the inhibition of cell invasion and migration. Luciferase reporter assay, chromatin immunoprecipitation assay, and Western blot analysis showed that ADAM17 could suppress the promoter activity and expression of miR‐449b‐3p by inducing NF‐κB transcriptional activity. In conclusion, our study provided new insights into the underlying mechanism of the invasion and metastasis of NPC. The novel miR‐449b‐3p/ADAM17/NF‐κB feedback loop could be a target for the clinical treatment of NPC.