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Epigenetic mechanism of survivin dysregulation in human cancer

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Abstract

Survivin (coding gene BIRC5) is a dual functional protein acting as a critical inhibitor of apoptosis (IAP) and key regulator of cell cycle progression. It is usually produced in embryonic tissues during development and undetectable in most adult tissues. Overexpression of Survivin frequently occurs in various human cancers and increased Survivin correlates with poor clinic outcome, tumor recurrence, and therapeutic resistance. Because of its selective expression in tumor, but not normal tissues, Survivin has been recognized as an attractive target for cancer treatment. Although several therapeutic approaches targeting Survivin are actively under clinical trials in human cancers, to date no Survivin-targeted therapy has been approved for cancer treatment. Numerous studies have devoted to uncovering the underlying mechanism resulting in Survivin dysregulation at multiple levels, such as transcriptional and post-transcriptional regulation. The current article provides a literature review on the transcriptional and epigenetic regulation of Survivin expression in human cancers. We focus on the impact of DNA methylation and histone modifications, including specific lysine methylation, demethylation, and acetylation on the expression of Survivin. The latest development of epigenetic approaches targeting Survivin for cancer treatment are also discussed.

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Acknowledgements

This work was supported by the National Institutes of Health/National Cancer Institute (NIH/NCI) (R01CA201011) and the National Natural Science Foundation of China (81472763 to Bolin Liu).

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Correspondence to Zhimin He or Bolin Liu.

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Lyu, H., Huang, J., He, Z. et al. Epigenetic mechanism of survivin dysregulation in human cancer. Sci. China Life Sci. 61, 808–814 (2018). https://doi.org/10.1007/s11427-017-9230-2

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