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浙江大学学报(医学版)  2021, Vol. 50 Issue (1): 1-16    DOI: 10.3724/zdxbyxb-2021-0053
专题报道     
表观遗传与肿瘤代谢研究进展
韩恒毅(),冯帆,李海涛()
清华大学医学院,北京 100084
Research advances on epigenetics and cancer metabolism
HAN Hengyi(),FENG Fan,LI Haitao()
School of Medicine,Tsinghua University,Beijing 100084,China
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摘要:

表观遗传学主要关注DNA甲基化、组蛋白修饰、染色质重塑,以及非编码RNA等超越DNA序列的基因调控机制。表观遗传机制参与了个体发育、细胞命运决定和肿瘤发生等众多生物学过程。其中表观遗传信息以各种染色质修饰和高级结构的形式存储于基因组中,它的建立和维持与细胞代谢紧密相关。肿瘤细胞中存在的代谢改变包括有氧糖酵解、葡萄糖摄取量增加、谷氨酰胺代谢异常活跃、利用非主要供能物质供能等,这些改变满足了肿瘤发生发展过程中旺盛的能量和物质需求,帮助细胞适应缺氧的肿瘤微环境,进而为肿瘤增殖、侵袭、迁移等生物活动提供支持。肿瘤细胞的表观遗传修饰与代谢之间存在复杂的相互关系,一方面肿瘤细胞中的代谢产物作为表观修饰酶的辅因子、修饰供体或拮抗分子影响表观修饰景观;另一方面表观遗传修饰可以直接改变代谢酶和转运蛋白的表达或通过影响信号转导和转录因子的表达调控细胞代谢。本文综述了不同表观遗传学过程与肿瘤细胞代谢之间的相互作用,并展望两者在肿瘤治疗中的潜在应用前景。

关键词: 表观遗传学代谢肿瘤DNA甲基化组蛋白修饰非编码RNA表观景观综述    
Abstract:

Epigenetics concerns gene regulatory mechanisms beyond DNA sequence,such as DNA methylation,histone modification,chromatin remodeling,and non-coding RNA. Epigenetic mechanisms play a key role in development,cell fate decision and tumorigenesis. Chromatin modifications and its high order structure across our genome are major forms of epigenetic information,and its establishment and maintenance are closely related to cell metabolism. Metabolic changes in cancer cells include aerobic glycolysis,increased glucose uptake,abnormally active glutamine metabolism,and the use of non-conventional energy supply. These changes meet the vigorous energy and matter needs for the development and spread of cancer,and help tumor cells adapt to hypoxia microenvironment for their survival,proliferation,invasion and migration. There is a complex relationship between epigenetic modifications and cell metabolism in tumor. On the one hand,metabolites in tumor cells may act as cofactors,modification donors or antagonists of epigenetic enzymes,thus modulating the epigenetic landscape. On the other hand,epigenetic modifications can directly regulate the expression of metabolic enzymes,transporters,signaling pathway and transcription factors to affect cell metabolism. This article reviews the crosstalk between epigenetics and cancer metabolism,to explore their potential future applications in the treatment of tumors.

Key words: Epigenetics    Metabolism    Tumor    DNA methylation    Histone modification    Non-coding RNA    Epigenetic landscape    Review
收稿日期: 2021-01-12 出版日期: 2021-05-14
CLC:  R730.23  
基金资助: 国家重点研发计划(2020YFA0803300)
通讯作者: 李海涛     E-mail: hanhy17@mails.tsinghua.edu.cn;lht@tsinghua.edu.cn
作者简介: 韩恒毅,博士研究生,主要从事表观遗传和肿瘤生物学研究;E-mail:hanhy17@mails.tsinghua.edu.cn;https://orcid.org/0000-0003-4840-4293.冯 帆,博士后,主要从事表观遗传调控的分子机制研究;E-mail:fengfan8@mails. tsinghua.edu.cn; https://orcid.org/0000-0001-8345-2894
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韩恒毅,冯帆,李海涛. 表观遗传与肿瘤代谢研究进展[J]. 浙江大学学报(医学版), 2021, 50(1): 1-16.

HAN Hengyi,FENG Fan,LI Haitao. Research advances on epigenetics and cancer metabolism. J Zhejiang Univ (Med Sci), 2021, 50(1): 1-16.

链接本文:

http://www.zjujournals.com/med/CN/10.3724/zdxbyxb-2021-0053        http://www.zjujournals.com/med/CN/Y2021/V50/I1/1

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