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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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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
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author 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
author_facet 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
author_sort Fei, Qian
collection PubMed
description 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.
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spelling pubmed-67924932019-10-21 Feedback loop in miR‐449b‐3p/ADAM17/NF‐κB promotes metastasis in nasopharyngeal carcinoma 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 Cancer Med Cancer Biology 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. John Wiley and Sons Inc. 2019-08-21 /pmc/articles/PMC6792493/ /pubmed/31433128 http://dx.doi.org/10.1002/cam4.2469 Text en © 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Cancer Biology
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
Feedback loop in miR‐449b‐3p/ADAM17/NF‐κB promotes metastasis in nasopharyngeal carcinoma
title Feedback loop in miR‐449b‐3p/ADAM17/NF‐κB promotes metastasis in nasopharyngeal carcinoma
title_full Feedback loop in miR‐449b‐3p/ADAM17/NF‐κB promotes metastasis in nasopharyngeal carcinoma
title_fullStr Feedback loop in miR‐449b‐3p/ADAM17/NF‐κB promotes metastasis in nasopharyngeal carcinoma
title_full_unstemmed Feedback loop in miR‐449b‐3p/ADAM17/NF‐κB promotes metastasis in nasopharyngeal carcinoma
title_short Feedback loop in miR‐449b‐3p/ADAM17/NF‐κB promotes metastasis in nasopharyngeal carcinoma
title_sort feedback loop in mir‐449b‐3p/adam17/nf‐κb promotes metastasis in nasopharyngeal carcinoma
topic Cancer Biology
url 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
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