Li Qiao, Zhu Qingsan
Department of Orthopedic Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China.
Department of Spine Surgery, The First Hospital of Jilin University, Changchun, Jilin, China.
Front Oncol. 2023 Mar 16;13:1153463. doi: 10.3389/fonc.2023.1153463. eCollection 2023.
The AlkB family (ALKBH1-8 and FTO), a member of the Fe (II)- and α-ketoglutarate-dependent dioxygenase superfamily, has shown the ability to catalyze the demethylation of a variety of substrates, including DNA, RNA, and histones. Methylation is one of the natural organisms' most prevalent forms of epigenetic modifications. Methylation and demethylation processes on genetic material regulate gene transcription and expression. A wide variety of enzymes are involved in these processes. The methylation levels of DNA, RNA, and histones are highly conserved. Stable methylation levels at different stages can coordinate the regulation of gene expression, DNA repair, and DNA replication. Dynamic methylation changes are essential for the abilities of cell growth, differentiation, and division. In some malignancies, the methylation of DNA, RNA, and histones is frequently altered. To date, nine AlkB homologs as demethylases have been identified in numerous cancers' biological processes. In this review, we summarize the latest advances in the research of the structures, enzymatic activities, and substrates of the AlkB homologs and the role of these nine homologs as demethylases in cancer genesis, progression, metastasis, and invasion. We provide some new directions for the AlkB homologs in cancer research. In addition, the AlkB family is expected to be a new target for tumor diagnosis and treatment.
AlkB家族（ALKBH1 - 8和FTO）是Fe（II）和α-酮戊二酸依赖性双加氧酶超家族的成员，已显示出催化多种底物（包括DNA、RNA和组蛋白）去甲基化的能力。甲基化是天然生物体中最普遍的表观遗传修饰形式之一。遗传物质上的甲基化和去甲基化过程调节基因转录和表达。这些过程涉及多种酶。DNA、RNA和组蛋白的甲基化水平高度保守。不同阶段稳定的甲基化水平可协调基因表达、DNA修复和DNA复制的调控。动态甲基化变化对于细胞生长、分化和分裂能力至关重要。在一些恶性肿瘤中，DNA、RNA和组蛋白的甲基化经常发生改变。迄今为止，已在多种癌症的生物学过程中鉴定出九种作为去甲基酶的AlkB同源物。在本综述中，我们总结了AlkB同源物在结构、酶活性和底物研究方面的最新进展，以及这九种同源物作为去甲基酶在癌症发生、发展、转移和侵袭中的作用。我们为AlkB同源物在癌症研究中提供了一些新方向。此外，AlkB家族有望成为肿瘤诊断和治疗的新靶点。
