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Regulation of IKKβ by miR-199a affects NF-κB activity in ovarian cancer cells

Oncogene volume 27, pages 4712–4723 (2008)Cite this article

Abstract

Cancer progression is an abnormal form of tissue repair characterized by chronic inflammation. IκB kinase-β (IKKβ) required for nuclear factor-κB (NF-κB) activation plays a critical role in this process. Using EOC cells isolated from malignant ovarian cancer ascites and solid tumors, we identified IKKβ as a major factor promoting a functional TLR–MyD88–NF-κB pathway that confers to EOC cell the capacity to constitutively secrete proinflammatory/protumor cytokines and therefore promoting tumor progression and chemoresistance. Furthermore, we describe for the first time the identification of the microRNA hsa-miR-199a as a regulator of IKKβ expression. Our study describes the property of ovarian cancer cells to enhance the inflammatory microenvironment as a result of the expression of an active IKKβ pathway. Identification of these markers in patients' tumor samples may facilitate the adequate selection of treatment and open new venues for the development of effective therapy for chemoresistant ovarian cancers.

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Acknowledgements

This study was supported in part by funds from the Discovery to Cure Program, Nicholas Brady and Sands Foundation. We thank the support of Drs Mark Landers, Amy Cumeo and Heather White from Invitrogen on the micro-RNA studies. We thank Dr Yung-Chi Cheng from Pharmacology Department, Yale University for providing Eriocalyxin B. We also thank Dr Sankar Ghosh from Immunology Department, Yale University for sharing pBIIX-LUC.

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Authors and Affiliations

  1. Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT, USA

    R Chen

  2. Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA

    R Chen, A B Alvero, D A Silasi, M G Kelly, S Fest, I Visintin, A Leiser, P E Schwartz, T Rutherford & G Mor

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  1. R Chen
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Correspondence to G Mor.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Chen, R., Alvero, A., Silasi, D. et al. Regulation of IKKβ by miR-199a affects NF-κB activity in ovarian cancer cells. Oncogene 27, 4712–4723 (2008). https://doi.org/10.1038/onc.2008.112

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