Hosseini Amir, Minucci Saverio
Department of Experimental Oncology, European Institute of Oncology, Milan, Italy.
Department of Biosciences, University of Milan, Milan, Italy.
Epigenomics. 2017 Aug;9(8):1123-1142. doi: 10.2217/epi-2017-0022. Epub 2017 Jul 12.
Histone methylation plays a key role in the regulation of chromatin structure, and its dynamics regulates important cellular processes. The investigation of the role of alterations in histone methylation in cancer has led to the identification of histone methyltransferases and demethylases as promising novel targets for therapy. Lysine-specific demethylase 1(LSD1, also known as KDM1A) is the first discovered histone lysine demethylase, with the ability to demethylase H3K4me1/2 and H3K9me1/2 at target loci in a context-dependent manner. LSD1 regulates the balance between self-renewal and differentiation of stem cells, and is highly expressed in various cancers, playing an important role in differentiation and self-renewal of tumor cells. In this review, we summarize recent studies about the LSD1, its role in normal and tumor cells, and the potential use of small molecule LSD1 inhibitors in therapy.
组蛋白甲基化在染色质结构调控中起关键作用，其动态变化调控着重要的细胞过程。对组蛋白甲基化改变在癌症中作用的研究已导致组蛋白甲基转移酶和去甲基酶被确定为有前景的新型治疗靶点。赖氨酸特异性去甲基酶1（LSD1，也称为KDM1A）是首个被发现的组蛋白赖氨酸去甲基酶，能够以上下文依赖的方式使靶位点的H3K4me1/2和H3K9me1/2去甲基化。LSD1调节干细胞自我更新与分化之间的平衡，在多种癌症中高表达，在肿瘤细胞的分化和自我更新中发挥重要作用。在本综述中，我们总结了关于LSD1的最新研究、其在正常细胞和肿瘤细胞中的作用以及小分子LSD1抑制剂在治疗中的潜在用途。
