An Epigenetic Role of Mitochondria in Cancer.

An Epigenetic Role of Mitochondria in Cancer.
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线粒体在癌症中的表观遗传作用

DOI:
10.3390/cells11162518
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发表时间:
2022-08-13
期刊:
影响因子:
6
通讯作者:
--
中科院分区:
生物学2区
文献类型:
--
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线粒体不仅是主要的能量供应者,也是细胞代谢中心,调控着表观遗传调控中的多种关键代谢产物。这些代谢物包括乙酰辅酶A、α-酮戊二酸(α-KG)、S-腺苷甲硫氨酸(SAM)、NAD+和O-连接β-N-乙酰葡糖胺(O-GlcNAc),它们是DNA甲基化和组蛋白翻译后修饰的主要底物,对基因转录调控和细胞命运决定至关重要。肿瘤的发生归因于多种因素,包括基因突变和肿瘤微环境。线粒体和表观遗传学在肿瘤的发生、发展、转移和复发中起重要作用。靶向线粒体代谢和表观遗传学是肿瘤治疗的有前途的治疗策略。在这篇综述中,我们总结了线粒体在表观遗传修饰所需的关键代谢物和细胞命运调节中的作用,并讨论了通过靶向表观遗传修饰剂和代谢调节中的相关酶来治疗癌症的当前策略。这一审查是一个重要的贡献,了解目前的代谢表观遗传肿瘤的概念。
Mitochondria are not only the main energy supplier but are also the cell metabolic center regulating multiple key metaborates that play pivotal roles in epigenetics regulation. These metabolites include acetyl-CoA, α-ketoglutarate (α-KG), S-adenosyl methionine (SAM), NAD+, and O-linked beta-N-acetylglucosamine (O-GlcNAc), which are the main substrates for DNA methylation and histone post-translation modifications, essential for gene transcriptional regulation and cell fate determination. Tumorigenesis is attributed to many factors, including gene mutations and tumor microenvironment. Mitochondria and epigenetics play essential roles in tumor initiation, evolution, metastasis, and recurrence. Targeting mitochondrial metabolism and epigenetics are promising therapeutic strategies for tumor treatment. In this review, we summarize the roles of mitochondria in key metabolites required for epigenetics modification and in cell fate regulation and discuss the current strategy in cancer therapies via targeting epigenetic modifiers and related enzymes in metabolic regulation. This review is an important contribution to the understanding of the current metabolic-epigenetic-tumorigenesis concept.
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