Zhuo Chuanjun, Wang Dawei, Zhou Chunhua, Chen Ce, Li Jie, Tian Hongjun, Li Shen, Ji Feng, Liu Chuanxin, Chen Min, Zhang Li
Genetics Laboratory, Department of Neuroimaging, Department of Psychiatry, Nankai University Affiliated Anding Hospital, Tianjin Anding Hospital, Tianjin, China.
Psychiatric Genetic Laboratory, Department of Psychiatry, Jining Medical University, Jining, China.
Front Mol Neurosci. 2019 Feb 12;12:1. doi: 10.3389/fnmol.2019.00001. eCollection 2019.
Schizophrenia (SCZ) is a common psychiatric disorder with polygenetic pathogenesis. Among the many identified candidate genes and loci, the group of tumour suppressor genes has drawn our interest. In this mini-review article, we describe evidence of a correlation between major tumour suppressor genes and SCZ development. Genetic mutations ranging from single nucleotide polymorphisms to large structural alterations have been found in tumour-related genes in patients with SCZ. Epigenetic mechanisms, including DNA methylation/acetylation and microRNA regulation of tumour suppressor genes, have also been implicated in SCZ. Beyond genetic correlations, we hope to establish causal relationships between tumour suppressor gene function and SCZ risk. Accumulating evidence shows that tumour suppressor genes may mediate cell survival and neural development, both of which contribute to SCZ aetiology. Moreover, converging intracellular signalling pathways indicate a role of tumour suppressor genes in SCZ pathogenesis. Tumour suppressor gene function may mediate a direct link between neural development and function and psychiatric disorders, including SCZ. A deeper understanding of how neural cell development is affected by tumour suppressors may lead to improved anti-psychotic drugs.
精神分裂症（SCZ）是一种具有多基因发病机制的常见精神疾病。在众多已确定的候选基因和基因座中，肿瘤抑制基因群体引起了我们的关注。在这篇小型综述文章中，我们描述了主要肿瘤抑制基因与SCZ发生之间相关性的证据。在SCZ患者的肿瘤相关基因中发现了从单核苷酸多态性到大型结构改变的基因突变。表观遗传机制，包括DNA甲基化/乙酰化和肿瘤抑制基因的微小RNA调控，也与SCZ有关。除了基因相关性之外，我们希望建立肿瘤抑制基因功能与SCZ风险之间的因果关系。越来越多的证据表明，肿瘤抑制基因可能介导细胞存活和神经发育，这两者都与SCZ的病因有关。此外，趋同的细胞内信号通路表明肿瘤抑制基因在SCZ发病机制中起作用。肿瘤抑制基因功能可能介导神经发育和功能与包括SCZ在内的精神疾病之间的直接联系。更深入地了解肿瘤抑制因子如何影响神经细胞发育可能会带来更好的抗精神病药物。
