Nejati-Koshki Kazem, Roberts Chris-Tiann, Babaei Ghader, Rastegar Mojgan
Pharmaceutical Sciences Research Center, Ardabil University of Medical Sciences, Ardabil 85991-56189, Iran.
Department of Biochemistry and Medical Genetics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0J9, Canada.
Cancers (Basel). 2023 May 9;15(10):2683. doi: 10.3390/cancers15102683.
Epigenetic mechanisms are gene regulatory processes that control gene expression and cellular identity. Epigenetic factors include the "writers", "readers", and "erasers" of epigenetic modifications such as DNA methylation. Accordingly, the nuclear protein Methyl-CpG-Binding Protein 2 (MeCP2) is a reader of DNA methylation with key roles in cellular identity and function. Research studies have linked altered DNA methylation, deregulation of MeCP2 levels, or gene mutations to different types of human disease. Due to the high expression level of MeCP2 in the brain, many studies have focused on its role in neurological and neurodevelopmental disorders. However, it is becoming increasingly apparent that MeCP2 also participates in the tumorigenesis of different types of human cancer, with potential oncogenic properties. It is well documented that aberrant epigenetic regulation such as altered DNA methylation may lead to cancer and the process of tumorigenesis. However, direct involvement of MeCP2 with that of human cancer was not fully investigated until lately. In recent years, a multitude of research studies from independent groups have explored the molecular mechanisms involving MeCP2 in a vast array of human cancers that focus on the oncogenic characteristics of MeCP2. Here, we provide an overview of the proposed role of MeCP2 as an emerging oncogene in different types of human cancer.
表观遗传机制是控制基因表达和细胞特性的基因调控过程。表观遗传因子包括DNA甲基化等表观遗传修饰的“书写者”“阅读者”和“擦除者”。因此,核蛋白甲基-CpG-结合蛋白2(MeCP2)是DNA甲基化的阅读者,在细胞特性和功能中起关键作用。研究已将DNA甲基化改变、MeCP2水平失调或基因突变与不同类型的人类疾病联系起来。由于MeCP2在大脑中的高表达水平,许多研究聚焦于其在神经和神经发育障碍中的作用。然而,越来越明显的是,MeCP2也参与不同类型人类癌症的肿瘤发生,具有潜在的致癌特性。有充分证据表明,异常的表观遗传调控,如DNA甲基化改变,可能导致癌症和肿瘤发生过程。然而,直到最近,MeCP2与人类癌症的直接关联才得到充分研究。近年来,来自多个独立研究小组的大量研究探索了MeCP2在众多人类癌症中的分子机制,这些研究聚焦于MeCP2的致癌特性。在此,我们概述了MeCP2作为一种新兴致癌基因在不同类型人类癌症中所起的作用。