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RNA aptamers interfering with nucleophosmin oligomerization induce apoptosis of cancer cells

Oncogene volume 28, pages 4201–4211 (2009)Cite this article

Abstract

Nucleophosmin (NPM) is a multifunctional protein involved in both proliferation and apoptosis. Importantly, NPM negatively regulates p53 and is frequently overexpressed in a wide variety of cancers. To identify inhibitory molecules of NPM, we used an in vitro selection method termed systematic evolution of ligands by exponential enrichment (SELEX) to select RNA aptamers that bind to NPM with high affinity and specificity. The selected RNA aptamers bind to the central acidic region of NPM and affect its oligomerization both in vitro and in vivo. Remarkably, expression of NPM-specific aptamers causes mislocalization of NPM in the nucleoplasm rather than in the nucleolus, suggesting that NPM oligomerization is important for its proper localization. Moreover, p14ARF is mislocalized in the nucleoplasm and p53 is upregulated in cells expressing NPM aptamers. In addition, cancer cells expressing NPM aptamers not only undergo apoptosis on their own, but are more susceptible to apoptosis induced by DNA-damaging agents as well. These results suggest that interfering with NPM oligomerization can inhibit NPM function and aptamers targeting NPM can serve as potential lead for developing anticancer drugs.

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Acknowledgements

We thank Dr S Luo and Dr D Wu for providing NPM and p14ARF cDNAs; Dr Y Liu for help with protein purification; Dr X Wang for helpful suggestions and critical reading of the paper. This research was supported by grants from National 863 Program (no. 2006AA02Z147), National Basic Research Program (nos. 2006CB504100 and 2007CB947201), National Natural Science Foundation (no. 30871266) and Chinese Academy of Sciences (no. KSC1-YW-R-70). CY was supported by the CAS 100-Talents Program.

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Authors and Affiliations

  1. Key Laboratory of Molecular and Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China

    Y Jian, Z Gao, J Sun, Q Shen, Y Jing & C Yang

  2. National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China

    F Feng

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  1. Y Jian
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Correspondence to C Yang.

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Jian, Y., Gao, Z., Sun, J. et al. RNA aptamers interfering with nucleophosmin oligomerization induce apoptosis of cancer cells. Oncogene 28, 4201–4211 (2009). https://doi.org/10.1038/onc.2009.275

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