Department of Pathology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA.
Cancer Research Institute and Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou, 510095, China.
Sci China Life Sci. 2018 Jul;61(7):808-814. doi: 10.1007/s11427-017-9230-2. Epub 2018 Jan 4.
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（编码基因 BIRC5）是一种具有双重功能的蛋白质，可作为细胞凋亡（IAP）的关键抑制剂和细胞周期进程的关键调节剂。它通常在发育过程中的胚胎组织中产生，在大多数成年组织中无法检测到。Survivin 的过度表达经常发生在各种人类癌症中，并且 Survivin 的增加与不良临床结局、肿瘤复发和治疗耐药性相关。由于其在肿瘤中的选择性表达，但不在正常组织中，Survivin 已被认为是癌症治疗的有吸引力的靶标。尽管目前有几种针对 Survivin 的治疗方法正在人类癌症的临床试验中积极进行，但迄今为止，尚无针对 Survivin 的靶向治疗方法被批准用于癌症治疗。许多研究致力于揭示导致 Survivin 在多个水平（如转录和转录后调控）失调的潜在机制。本文综述了人类癌症中 Survivin 表达的转录和表观遗传调控。我们重点讨论了 DNA 甲基化和组蛋白修饰（包括特定赖氨酸的甲基化、去甲基化和乙酰化）对 Survivin 表达的影响。还讨论了针对 Survivin 的表观遗传治疗方法在癌症治疗中的最新进展。
