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Induction of apoptosis of non-small cell lung cancer by a methylated oligonucleotide targeting survivin gene

Cancer Gene Therapy volume 17, pages 441–446 (2010)Cite this article

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Abstract

Survivin overexpression is closely linked to lung oncogenesis. Silencing of survivin gene by molecular antagonists has shown promise as novel anticancer strategies. DNA methylation is a critical epigenetic modification that silences gene transcription. In this study, we used a new methylated oligonucleotide, which mediates sequence-specific DNA methylation in cell, as a strategic alternative to survivin-targeting treatment, and investigated its efficacy in suppressing survivin expression and the consequent apoptotic induction potential in NCI-H460 cells. SurKex1, a methylated sense oligonucleotide, was shown to reduce specifically survivin mRNA expression and induce cell apoptosis. In addition, it has been supposed that the methylated oligonucleotide exerts its effect of gene silencing through the activation of DNA methyltransferase (DNMT1), but the exact mechanism is still unknown. Our data suggest for the first time that the SurKex1 exerts its down-regulatory effects on survivin expression through the activation of DNMT1.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (Grant No. 30471612), and the Major Program of the Shanghai Committee of Science and Technology (Grant No. 04DZ19211). We thank Zhou Xiangjun and Wang Yongxiang for Surkex1 design and provision.

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  1. School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China

    H L Li & A N Ma

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Correspondence to H L Li.

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Li, H., Ma, A. Induction of apoptosis of non-small cell lung cancer by a methylated oligonucleotide targeting survivin gene. Cancer Gene Ther 17, 441–446 (2010). https://doi.org/10.1038/cgt.2009.82

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