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TWISTing stemness, inflammation and proliferation of epithelial ovarian cancer cells through MIR199A2/214

Oncogene volume 29, pages 3545–3553 (2010)Cite this article

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Abstract

Cancer stem cells are responsible for sustaining the tumor and giving rise to proliferating and progressively differentiating cells. However, the molecular mechanisms regulating the process of cancer stem cell (CSC) differentiation is not clearly understood. Recently, we reported the isolation of the epithelial ovarian cancer (EOC) stem cells (type I/CD44+). In this study, we show that type I/CD44+ cells are characterized by low levels of both miR-199a and miR-214, whereas mature EOC cells (type II/CD44−) have higher levels of miR-199a and miR-214. Moreover, these two micro RNAs (miRNAs) are regulated as a cluster on pri-miR-199a2 within the human Dnm3os gene (GenBank FJ623959). This study identify Twist1 as a regulator of this unique miRNA cluster responsible for the regulation of the IKKβ/NF-κB and PTEN/AKT pathways and its association of ovarian CSC differentiation. Our data suggest that Twist1 may be an important regulator of ‘stemness’ in EOC cells. The regulation of MIR199A2/214 expression may be used as a potential therapeutic approach in EOC patients.

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Acknowledgements

This study was supported in part by grants from NCI/NIH RO1CA127913, RO1CA118678, the Janet Burros Memorial Foundation, the Sands Family Foundation and the Discovery To Cure Research Program.

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Author notes

  1. G Yin and R Chen: These authors contributed equally to this work.

Authors and Affiliations

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

    G Yin, R Chen, A B Alvero, H-H Fu, J Holmberg, T Rutherford & G Mor

  2. Neuroscience, Beckman Research Institute of the City of Hope, Duarte, CA, USA

    C Glackin

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  1. G Yin
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  2. R Chen
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  3. A B Alvero
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Correspondence to G Mor.

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Yin, G., Chen, R., Alvero, A. et al. TWISTing stemness, inflammation and proliferation of epithelial ovarian cancer cells through MIR199A2/214. Oncogene 29, 3545–3553 (2010). https://doi.org/10.1038/onc.2010.111

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