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Biomedicines 2018, 6(2), 40; https://doi.org/10.3390/biomedicines6020040

Roles of NF-κB Signaling in the Regulation of miRNAs Impacting on Inflammation in Cancer

1
Laboratory of Biology, School of Medicine, Faculty of Health Sciences, University of Ioannina, 45110 Ioannina, Greece
2
Biomedical Research Division, Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology, 45110 Ioannina, Greece
3
Department of Molecular Biology and Genetics, Democritus University of Thrace, 68100 Alexandroupolis, Greece
4
Biomedical Research Foundation of the Academy of Athens, 4 Soranou Ephessiou Street, 115-27 Athens, Greece
5
Departments of Biochemistry and Cell Biology, Microbiology and Pathology, Stony Brook University, Stony Brook, NY 11794-5215, USA
6
Department of Biology, San Diego State University, San Diego, CA 92182-4614, USA
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 5 March 2018 / Revised: 26 March 2018 / Accepted: 27 March 2018 / Published: 30 March 2018
(This article belongs to the Special Issue Roles of NF-κB in Cancer and Their Therapeutic Approaches)
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Abstract

The NF-κB family of transcription factors regulate the expression of genes encoding proteins and microRNAs (miRNA, miR) precursors that may either positively or negatively regulate a variety of biological processes such as cell cycle progression, cell survival, and cell differentiation. The NF-κB-miRNA transcriptional regulatory network has been implicated in the regulation of proinflammatory, immune, and stress-like responses. Gene regulation by miRNAs has emerged as an additional epigenetic mechanism at the post-transcriptional level. The expression of miRNAs can be regulated by specific transcription factors (TFs), including the NF-κB TF family, and vice versa. The interplay between TFs and miRNAs creates positive or negative feedback loops and also regulatory networks, which can control cell fate. In the current review, we discuss the impact of NF-κB-miRNA interplay and feedback loops and networks impacting on inflammation in cancer. We provide several paradigms of specific NF-κB-miRNA networks that can regulate inflammation linked to cancer. For example, the NF-κB-miR-146 and NF-κB-miR-155 networks fine-tune the activity, intensity, and duration of inflammation, while the NF-κB-miR-21 and NF-κB-miR-181b-1 amplifying loops link inflammation to cancer; and p53- or NF-κB-regulated miRNAs interconnect these pathways and may shift the balance to cancer development or tumor suppression. The availability of genomic data may be useful to verify and find novel interactions, and provide a catalogue of 162 miRNAs targeting and 40 miRNAs possibly regulated by NF-κB. We propose that studying active TF-miRNA transcriptional regulatory networks such as NF-κB-miRNA networks in specific cancer types can contribute to our further understanding of the regulatory interplay between inflammation and cancer, and also perhaps lead to the development of pharmacologically novel therapeutic approaches to combat cancer. View Full-Text
Keywords: miRNAs; NF-κB; transcriptional regulatory networks; oncogenic and tumor suppressor pathways; cancer; inflammation miRNAs; NF-κB; transcriptional regulatory networks; oncogenic and tumor suppressor pathways; cancer; inflammation
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Markopoulos, G.S.; Roupakia, E.; Tokamani, M.; Alabasi, G.; Sandaltzopoulos, R.; Marcu, K.B.; Kolettas, E. Roles of NF-κB Signaling in the Regulation of miRNAs Impacting on Inflammation in Cancer. Biomedicines 2018, 6, 40.

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