半胱氨酸双加氧酶1基因启动子甲基化在肿瘤研究中的应用  

Application of CDO1 Gene Promoter Methylation in Tumors

作　　者：周雨[1] 余红波 操媛 王俊杰[1] ZHOU Yu;YU Hong-Bo;CAO Yuan;WANG Jun-Jie(Affiliated Renhe Hospital of Three Gorges University,Institute of Gynecological Oncology,Three Gorges University,Yichang 443001China;Affiliated Renhe Hospital of Three Gorges University,Centre for Minimally Invasive Medicine,Three Gorges University,Yichang 443002,China;Affiliated Renhe Hospital of Three Gorges University,Institute of Female Pelvic Floor Disorders,Three Gorges University,Yichang 443002,China)

机构地区：[1]三峡大学附属仁和医院,三峡大学妇科肿瘤研究所,宜昌443001 [2]三峡大学附属仁和医院,三峡大学微无创医学研究中心,宜昌443002 [3]三峡大学附属仁和医院,三峡大学女性盆底疾病研究所,宜昌443002

出　　处：《生物化学与生物物理进展》2024年第5期1043-1053,共11页Progress In Biochemistry and Biophysics

基　　金：国家自然科学基金(81302269);湖北省教育厅科学技术研究计划指导性项目(B2021033);宜昌市科技创新基金(A23-1-062)资助。

摘　　要：半胱氨酸双加氧酶1(cysteine dioxygenase 1,CDO1)是一种肿瘤抑制基因(tumor suppressor gene,TSG),参与细胞增殖、分化、凋亡及铁死亡等一系列生理过程。DNA甲基化是人类肿瘤中表观遗传学修饰的主要方式之一,CDO1是一种与恶性肿瘤高度相关的甲基化基因(highly relevant methylation gene,HRMG),在多种人类癌症中被其甲基化启动子所沉默,甲基化的CDO1基因启动子是人类肿瘤中最常见的早期特异性诊断标志物之一。本文就CDO1生物学功能及其启动子DNA的甲基化在肿瘤中的作用及调控作一综述。Cysteine dioxygenase 1(CDO1)gene is a non-heme structured,iron-containing metalloenzyme involved in the conversion of cysteine to cysteine sulfinic acid to regulate cysteine accumulation in vivo.Elevated levels of cysteine have been shown to be cytotoxic and neurotoxic,and this is the first important step in the breakdown of cysteine metabolism in mammalian tissues.The human CDO1 gene is located on chromosome 5q23.2.Studies have shown that deletion or epigenetic silencing of this chromosomal region contributes to tumorigenesis.It is highly expressed in the liver and placenta,and weakly in the heart,brain and pancreas.CDO1 is a tumor suppressor gene(TSG)with a wide range of functions,which can be involved in various biological processes such as tumor cell proliferation,differentiation,apoptosis and iron death,thus affecting the tumor development.CDO1 is epigenetically regulated in human cancers,compared to normal tissues.The CDO1’s mRNA or protein expression levels were significantly down-regulated in tumor tissues,whereas promoter DNA methylation of the CDO1 gene usually accumulates with the progression of human cancers.Aberrant hypermethylation on the CDO1 promoter is a common event in tumor cells,which leads to transcriptional inactivation and silencing of the CDO1 gene.High frequency of methylation of CDO1 gene promoter methylation region in a variety of tumors including breast,oesophageal,lung,bladder,gastric and colorectal cancers.CDO1 gene promoter methylation levels reflect cancer progression and malignant tumorigenesis,which is a common molecular indicator explaining poor prognosis in human cancers.Treatment with 5-aza-2′-deoxycytidine(a drug that promotes demethylation)reactivated the CDO1 expression in most cancer cell lines,indicating that the transcriptional expression of CDO1 is closely correlated with its promoter methylation level,CDO1 gene promoter methylation and tumor progression have also received increasing attention from researchers.It was found that CDO1 gene promoter hypermethylation ca

关 键 词：CDO1 肿瘤抑制基因 DNA甲基化 肿瘤 

分 类 号：Q2[生物学—细胞生物学] Q78