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伏马菌素B可诱导人胶质母细胞瘤U87MG细胞发生全基因组DNA高甲基化。

Fumonisin B induces global DNA hypermethylation in human glioblastoma U87MG cells.

作者信息

Foolchand Ashmika, Ghazi Terisha, Chuturgoon Anil A

机构信息

Discipline of Medical Biochemistry, School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa.

出版信息

Epigenetics. 2025 Dec;20(1):2523690. doi: 10.1080/15592294.2025.2523690. Epub 2025 Jun 26.

DOI:10.1080/15592294.2025.2523690
PMID:40566980
Abstract

Fumonisin B (FB) is a common maize contaminant known to induce toxicity and carcinogenesis in humans and animals; however, its epigenetic mechanisms remain poorly understood. DNA methylation is an epigenetic modification that controls gene expression through DNA methyltransferase and demethylase activities. In this study, the effect of FB on DNA methylation in brain glioblastoma U87MG cells was evaluated. FB cytotoxicity was determined by the MTT assay and an IC value of 880 µM FB was obtained. The ELISA-based global DNA methylation assay displayed an increase in 5-methylcytosine levels. qPCR and western blot revealed a significant increase in DNA methyltransferase expressions (DNMT1, DNMT3A, and DNMT3B) and a significant decrease in demethylase expression (MBD2). This data indicates that FB induces global DNA hypermethylation, through increased DNA methyltransferase expressions and DNA demethylase suppression in U87MG cells, thus suggesting an alternative mechanism of toxicity.

摘要

伏马菌素B(FB)是一种常见的玉米污染物,已知会在人类和动物中诱发毒性和致癌作用;然而,其表观遗传机制仍知之甚少。DNA甲基化是一种表观遗传修饰,通过DNA甲基转移酶和去甲基酶的活性来控制基因表达。在本研究中,评估了FB对脑胶质母细胞瘤U87MG细胞中DNA甲基化的影响。通过MTT法测定FB细胞毒性,获得FB的IC值为880µM。基于ELISA的全基因组DNA甲基化检测显示5-甲基胞嘧啶水平升高。qPCR和蛋白质印迹显示DNA甲基转移酶表达(DNMT1、DNMT3A和DNMT3B)显著增加,而去甲基酶表达(MBD2)显著降低。该数据表明,FB通过增加U87MG细胞中DNA甲基转移酶的表达和抑制DNA去甲基酶,诱导全基因组DNA高甲基化,从而提示一种毒性的替代机制。

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The epigenetic mechanisms involved in the treatment resistance of glioblastoma.胶质母细胞瘤治疗耐药性涉及的表观遗传机制。
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Methyl-CpG binding domain 2 (Mbd2) is an epigenetic regulator of autism-risk genes and cognition.甲基化CpG 结合域蛋白 2(Mbd2)是自闭症风险基因和认知的表观遗传调控因子。
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