Hua Chunyan, Chen Jiaqing, Li Shuting, Zhou Jianan, Fu Jiahong, Sun Weijian, Wang Wenqian
School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, China.
Wenzhou Medical University, Wenzhou, China.
Front Oncol. 2021 Dec 7;11:779918. doi: 10.3389/fonc.2021.779918. eCollection 2021.
Cancer therapy is moving beyond traditional chemotherapy to include epigenetic approaches. KDM6 demethylases are dynamic regulation of gene expression by histone demethylation in response to diverse stimuli, and thus their dysregulation has been observed in various cancers. In this review, we first briefly introduce structural features of KDM6 subfamily, and then discuss the regulation of KDM6, which involves the coordinated control between cellular metabolism (intrinsic regulators) and tumor microenvironment (extrinsic stimuli). We further describe the aberrant functions of KDM6 in human cancers, acting as either a tumor suppressor or an oncoprotein in a context-dependent manner. Finally, we propose potential therapy of KDM6 enzymes based on their structural features, epigenetics, and immunomodulatory mechanisms, providing novel insights for prevention and treatment of cancers.
癌症治疗正在超越传统化疗，纳入表观遗传学方法。KDM6去甲基化酶通过响应多种刺激的组蛋白去甲基化对基因表达进行动态调控，因此在各种癌症中都观察到了它们的失调。在本综述中，我们首先简要介绍KDM6亚家族的结构特征，然后讨论KDM6的调控，这涉及细胞代谢（内在调节因子）和肿瘤微环境（外在刺激）之间的协同控制。我们进一步描述了KDM6在人类癌症中的异常功能，它在不同情况下既可以作为肿瘤抑制因子，也可以作为癌蛋白。最后，我们基于KDM6酶的结构特征、表观遗传学和免疫调节机制提出了潜在的治疗方法，为癌症的预防和治疗提供了新的见解。
