MicroRNA-365a-3p inhibits c-Rel-mediated NF-[kappa] B signaling and the progression of pancreatic cancer

NF-κB contributes to the aggressiveness of pancreatic ductal adenocarcinoma (PDA), which is counteracted by the bioactive agent sulforaphane. We investigated sulforaphane-induced microRNA signaling and its influence on progression features. Using established cell lines, microRNA and gene arrays, we...

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Main Authors: Yin, Libo (Author) , Xiao, Xi (Author) , Georgikou, Christina (Author) , Yin, Yefeng (Author) , Liu, Li (Author) , Karakhanova, Svetlana (Author) , Luo, Yiqiao (Author) , Gladkich, Jury (Author) , Fellenberg, Jörg (Author) , Sticht, Carsten (Author) , Gretz, Norbert (Author) , Gross, Wolfgang (Author) , Herr, Ingrid (Author)
Format: Article (Journal)
Language:English
Published: 23 March 2019
In: Cancer letters
Year: 2019, Volume: 452, Pages: 203-212
ISSN:1872-7980
DOI:10.1016/j.canlet.2019.03.025
Online Access:Verlag, Volltext: https://doi.org/10.1016/j.canlet.2019.03.025
Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S0304383519301818
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Author Notes:Libo Yin, Xi Xiao, Christina Georgikou, Yefeng Yin, Li Liu, Svetlana Karakhanova, Yiqiao Luo, Jury Gladkich, Joerg Fellenberg, Carsten Sticht, Norbert Gretz, Wolfgang Gross, Ingrid Herr
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Summary:NF-κB contributes to the aggressiveness of pancreatic ductal adenocarcinoma (PDA), which is counteracted by the bioactive agent sulforaphane. We investigated sulforaphane-induced microRNA signaling and its influence on progression features. Using established cell lines, microRNA and gene arrays, we predicted miR-365a as the top candidate for the sulforaphane-induced inhibition of the NF-κB subunit c-Rel. The lipofection of miR-365a-3p mimics inhibited the luciferase activity of a c-Rel 3′-UTR construct, as well as c-Rel expression, NF-κB activity, and tumor viability, migration, and clonogenicity, whereas apoptosis was induced. In vivo, miR-365a-3p reduced the volume of tumor xenografts and the expression of progression markers. In a tissue array, the expression of miR-365a-3p was absent in almost all 91 malignant tissues but not in 5 normal tissues, thus confirming the previous results. Our observations suggest that sulforaphane-induced miR-365a-3p expression inhibits NF-κB activity by downregulating c-Rel, which prevents the progression of PDA.
Item Description:Im Titel ist "kappa" als griechischer Buchstabe dargestellt
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Physical Description:Online Resource
ISSN:1872-7980
DOI:10.1016/j.canlet.2019.03.025