治疗S-adenosylmethionine会影响前列腺癌细胞中的组素甲基化
Arthur Mathes1, Merve Busra Duman2, Alexander Neumann2
1Cardiovascular Genomics and Epigenomics, European Center for Angioscience, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Gene
|October 22, 2023
概括
在前列腺癌细胞中,S-adenosylmethionine (SAM) 改变了组织蛋白甲基化. 这种表观遗传修饰会影响基因表达,潜在地抑制癌症的生长和进展.
科学领域:
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 分子瘤学分子瘤学
- 癌症生物学 癌症生物学
背景情况:
- 在体外,S-adenosylmethionine (SAM) 是已知的癌细胞增殖,迁移和入侵的抑制剂.
- 基于SAM抗癌作用的精确分子机制,特别是在前列腺癌中,尚未完全理解.
- 基质子修饰,特别是H3K4me3和H3K27me3,是前列腺癌发病和进展的关键调节者.
研究的目的:
- 调查S-adenosylmethionine (SAM) 治疗是否诱导前列腺癌细胞中H3K4me3和H3K27me3甲基化概况的变化.
- 为了将观察到的表观遗传变化与基因表达特征相关联,并确定相关的生物途径.
主要方法:
- 前列腺癌PC-3细胞用200μmol的S-adenosylmethionine (SAM) 进行治疗.
- 进行染色体免疫沉测序 (ChIP-seq) 来分析H3K4me3和H3K27me3甲基化模式.
- 用RNA测序 (RNA-Seq) 进行基因表达分析.
- 基因本体学 (GO) 术语丰富分析用于解释甲基化和表达变化的功能影响.
主要成果:
- 治疗SAM导致基因组甲基化发生显著变化,H3K27me3有236个不同甲基化的区域,H3K4me3.3有560个不同甲基化的区域.
- GO术语分析显示,抗癌生物过程,分子功能和途径的上调调节和下调调节.
- 整合ChIP-seq和RNA-seq数据,确定了35个上调和56个下调的基因,与改变的甲基化区域相关.
- 在这些基因中,有17个上调基因被确定为瘤抑制剂,45个下调基因被归类为瘤基因.
结论:
- S-adenosylmethionine (SAM) 治疗显著改变前列腺癌细胞中的H3K4me3和H3K27me3甲基化概况.
- 这些表观遗传变化具有生物学相关性,影响与瘤抑制和瘤发生相关的基因表达模式.
- 这些发现为SAM的抗癌潜力提供了机理性的见解,突出了它在前列腺癌内表观遗传调节中的作用.
相关概念视频
01:17Phase II Reactions: Methylation Reactions
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Methylation is a phase II biotransformation process involving the attachment of a methyl group to a substrate. Enzymes known as methyltransferases orchestrate this reaction.
The mechanism of methylation unfolds in two stages. The first stage sees a methyltransferase enzyme facilitating the transfer of a methyl group from S-adenosylmethionine (SAM) to the substrate, forming S-adenosylhomocysteine (SAH). The second stage involves further metabolism of SAH into homocysteine, which can be recycled...
The mechanism of methylation unfolds in two stages. The first stage sees a methyltransferase enzyme facilitating the transfer of a methyl group from S-adenosylmethionine (SAM) to the substrate, forming S-adenosylhomocysteine (SAH). The second stage involves further metabolism of SAH into homocysteine, which can be recycled...
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The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
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