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      NF-κB-modulated miR-130a targets TNF-α in cervical cancer cells

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          Abstract

          Background

          Nuclear factor-κB (NF-κB) induces a variety of biological processes through transcriptional gene control whose products are components in various signaling pathways. MicroRNAs are a small endogenous non-coding RNAs that regulate gene expression and are involved in tumorigenesis. Using human cervical cancer cell lines, this study aimed to investigate whether NF-κB could regulate miR-130a expression and the functions and targets of miR-130a.

          Methods

          We used the HeLa and C 33A cervical cancer cell lines that were transfected with NF-κB or miR-130a overexpression plasmids to evaluate their effects on cell growth. We utilized bioinformatics, a fluorescent reporter assay, qRT-PCR and Western blotting to identify downstream target genes.

          Results

          In HeLa and C 33A cells, NF-κB and miR-130a overexpression promoted cell growth, but genetic knockdowns suppressed growth. TNF-α was identified as a target of miR-130a by binding in a 3’-untranslated region (3’UTR) EGFP reporter assay and by Western blot analysis. Furthermore, low TNF-α concentrations stimulated NF-κB activity and then induced miR-130a expression, and TNF-α overexpression rescued the effects of miR-130a on cervical cancer cells.

          Conclusions

          Our findings indicate that TNF-α can activate NF-κB activity, which can reduce miR-130a expression, and that miR-130a targets and downregulates TNF-α expression. Hence, we shed light on the negative feedback regulation of NF-κB/miR-130a/TNF-α/NF-κB in cervical cancer and may provide insight into the carcinogenesis of cervical cancer.

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          Most cited references62

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          MAVS recruits multiple ubiquitin E3 ligases to activate antiviral signaling cascades

          RNA virus infections are detected by the RIG-I family of receptors, which induce type-I interferons through the mitochondrial protein MAVS. MAVS forms large prion-like polymers that activate the cytosolic kinases IKK and TBK1, which in turn activate NF-κB and IRF3, respectively, to induce interferons. Here we show that MAVS polymers recruit several TRAF proteins, including TRAF2, TRAF5, and TRAF6, through distinct TRAF-binding motifs. Mutations of these motifs that disrupted MAVS binding to TRAFs abrogated its ability to activate IRF3. IRF3 activation was also abolished in cells lacking TRAF2, 5, and 6. These TRAF proteins promoted ubiquitination reactions that recruited NEMO to the MAVS signaling complex, leading to the activation of IKK and TBK1. These results delineate the mechanism of MAVS signaling and reveal that TRAF2, 5, and 6, which are normally associated with NF-κB activation, also play a crucial role in IRF3 activation in antiviral immune responses. DOI: http://dx.doi.org/10.7554/eLife.00785.001
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            TNF: a master switch for inflammation to cancer.

            Chronic inflammation has long been associated with the development of cancer, ever since Rudolf Virchow's first observation that leukocytes were present in neoplastic tissue more than 130 years ago. Recent evidences have reignited the interest of cancer researchers in the exciting concept of an association between chronic inflammation and cancer. Tumor necrosis factor alpha (TNF-alpha), initially discovered as a result of its antitumor activity, has now been shown to be one of the major mediators of inflammation. Induced by a wide range of pathogenic stimuli, TNF-alpha induces other inflammatory mediators and proteases that orchestrate inflammatory responses. TNF-alpha is also produced by tumors and can act as an endogenous tumor promoter. The role of TNF-alpha has been linked to all steps involved in tumorigenesis, including cellular transformation, promotion, survival, proliferation, invasion, angiogenesis, and metastasis. How TNF-alpha acts as a masterswitch in establishing an intricate link between inflammation and cancer is the focus of this review.
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              Tumor necrosis factor (TNF).

              S L Old (1985)
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                Author and article information

                Contributors
                Journal
                J Transl Med
                J Transl Med
                Journal of Translational Medicine
                BioMed Central
                1479-5876
                2014
                1 June 2014
                : 12
                : 155
                Affiliations
                [1 ]Tianjin Life Science Research Center and School of Basic Medical Sciences, Tianjin Medical University, No. 22 Qi-Xiang-Tai Road, Tianjin 300070, China
                [2 ]Tianjin Central Hospital of Gynecology Obstetrics, Tianjin, China
                Article
                1479-5876-12-155
                10.1186/1479-5876-12-155
                4084577
                24885472
                f5e332a9-e57e-476a-b637-10bde8429c53
                Copyright © 2014 Zhang et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 28 December 2013
                : 20 May 2014
                Categories
                Research

                Medicine
                mirna,mirna-130a,nf-κb,cervical cancer,tnf-α
                Medicine
                mirna, mirna-130a, nf-κb, cervical cancer, tnf-α

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