SETDB1 in cancer: overexpression and its therapeutic implications.
SETDB1 in cancer: overexpression and its therapeutic implications.
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发表时间：
2021
影响因子：
5.3
通讯作者：
Vanessa J Lazaro-Camp;Kiarash Salari;Xiangbing Meng;Shujie Yang
中科院分区：
文献类型：
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作者：
Vanessa J Lazaro-Camp;Kiarash Salari;Xiangbing Meng;Shujie Yang
SET Domain Bifurcated Histone Lysine Methyltransferase 1（SETDB 1，ESET，KMT 1 E）是一种参与基因沉默的H3 K9甲基转移酶。近年来，SETDB 1被认为是多种癌症中的癌基因，这突出了更好地理解SETDB 1扩增、过表达和激活的机制的迫切需要。在下面的综述中，我们首先研究了SETDB 1的历史，从1999年发现开始，到最近的发现结束。我们随后概述了SETDB 1的结构和亚细胞位置，以及调节其核转运的潜在机制。随后，我们介绍了SETDB 1的各种功能，包括它在早幼粒细胞白血病核体（PML-NB）形成中的作用，Akt的甲基化和激活，雄激素受体（AR）基因的沉默，逆转录酶抑制因子沉默，肿瘤抑制因子p53的抑制，以及它在促进肠分化和存活中的作用。癌细胞系百科全书（CCLE）在796个癌细胞系中筛选了SETDB 1依赖性，确定SETDB 1是其中531个细胞系的共同必需基因，这表明SETDB 1表达对于大多数癌症的生存至关重要。因此，我们提供了一个详细的审查乳腺癌，非小细胞肺癌，前列腺癌，结直肠癌，急性髓性白血病，神经胶质瘤，黑色素瘤，胰腺导管腺癌，肝癌，鼻咽癌，胃癌和子宫内膜癌的致癌作用。因此，我们回顾了几种已经用于靶向SETDB 1的方法，例如使用Mithramycin A，Mithramycin EC-8042，3 '-deazaneplanocin A（DZNep）和紫杉醇。最后，我们通过强调围绕SETDB 1的知识和挑战的剩余差距来结束。最后，我们的综述涵盖了关于SETDB 1的历史、功能及其在癌症中的意义的广泛研究结果，并为该领域未来的研究提供了建议。
SET Domain Bifurcated Histone Lysine Methyltransferase 1 (SETDB1, ESET, KMT1E) is a H3K9 methyltransferase involved in gene silencing. In recent years, SETDB1 has been implicated as an oncogene in various cancers, highlighting a critical need to better understand the mechanisms underlying SETDB1 amplification, overexpression, and activation. In the following review, we first examine the history of SETDB1, starting from its discovery in 1999 and ending with recent findings. We follow with an outline of the structure and subcellular location of SETDB1, as well as potential mechanisms for regulation of its nuclear transport. Subsequently, we introduce SETDB1's various functions, including its roles in promyelocytic leukemia nuclear body (PML-NB) formation, the methylation and activation of Akt, the silencing of the androgen receptor (AR) gene, retroelement silencing, the inhibition of tumor suppressor p53, and its role in promoting intestinal differentiation and survival. The Cancer Cell Line Encyclopedia (CCLE) screened SETDB1 dependency in 796 cancer cell lines, identifying SETDB1 as a common essential gene in 531 of them, demonstrating that SETDB1 expression is critical for the survival of the majority of cancers. Therefore, we provide a detailed review of the oncogenic effects of SETDB1 overexpression in breast cancer, non-small cell lung cancer, prostate cancer, colorectal cancer, acute myeloid leukemia, glioma, melanoma, pancreatic ductal adenocarcinoma, liver cancer, nasopharyngeal carcinoma, gastric carcinoma, and endometrial cancer. Accordingly, we review several methods that have been used to target SETDB1, such as using Mithramycin A, Mithralog EC-8042, 3'-deazaneplanocin A (DZNep), and paclitaxel. Finally, we conclude by highlighting remaining gaps in knowledge and challenges surrounding SETDB1. Ultimately, our review captures the wide scope of findings on SETDB1's history, function, its implications in cancer, and provides suggestions for future research in the field.