Epigenetic mechanism of Survivin dysregulation in human cancer  

作　　者：Hui Lyu Jingcao Huang Zhimin He Bolin Liu 

机构地区：[1]Department of Pathology,School of Medicine,University of Colorado Anschutz Medical Campus,Aurora,CO 80045,USA [2]Cancer Research Institute and Affiliated Cancer Hospital Guangzhou Medical University,Guangzhou 510095,China [3]Department of Hematology,Hematologic Research Laboratory,West China Hospital,Sichuan University,Chengdu 610041,China

出　　处：《Science China(Life Sciences)》2018年第7期808-814,共7页中国科学（生命科学英文版）

基　　金：supported by the National Institutes of Health/National Cancer Institute(NIH/NCI)(R01CA201011);the National Natural Science Foundation of China(81472763 to Bolin Liu)

摘　　要：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.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.

关 键 词：SURVIVIN EPIGENETICS DNA methylation histone modification cancer therapy 

分 类 号：R730[医药卫生—肿瘤]