铁死亡是一种新型的细胞程序性死亡方式,参与多种疾病的发生发展.对铁死亡调控机制的深入研究会帮助我们从新的角度去认识疾病的发生机制和探究潜在的药物干预靶点.因此,本文对铁死亡的表观遗传调控机制的最新研究进展进行了综述.研究发现,组蛋白的修饰如组蛋白甲基化、乙酰化和单泛素化等,能够通过激活或抑制铁死亡相关的溶质载体家族7成员11(recombinant solute carrier family 7 Member 11,SLC7A11)、谷胱甘肽过氧化物酶4(glutathione peroxidase 4,GPX4)等基因的转录进而调控铁死亡的发生.此外,DNA/RNA甲基化也影响着铁死亡的发生,如GPX4上游DNA甲基化的增加会导致脂质活性氧(reactive oxygen species,ROS)的积累从而促进细胞发生铁死亡.本文综述了近些年参与铁死亡调控的包括小分子RNA(microRNA)、长非编码RNA(long non-coding RNA,lncRNA)和环状RNA(circular RNA,circRNA)在内的非编码RNA的研究,发现非编码RNA也可以通过靶向调控谷胱甘肽(glutathione,GSH)合成、脂质ROS和GPX4活性等,在多种疾病尤其是肿瘤疾病的铁死亡过程中起举足轻重的作用.
The epigenetic regulatory mechanisms of ferroptosis
Ferroptosis is a new type of programmed cell death,which is involved in the occurrence and development of various diseases.In-depth research on the regulatory mechanism of ferroptosis will help us to understand the pathogenesis of the disease and inquiry potential drug intervention.Therefore,this paper reviews the latest research progress on the epigenetic regulation mechanism of ferroptosis.Studies have found that histone modifications,such as histone methylation,acetylation and mono-ubiquitin,can regulate ferroptosis by activating or inhibiting the transcription of ferroptosis-related genes such as recombinant solute carrier family 7 member 11(SLC7A11),glutathione peroxidase 4(GPX4).In addition,DNA/RNA methylation also affects the occurrence of ferroptosis.For example,the increase of DNA methylation upstream of GPX4 can lead to the accumulation of lipid reactive oxygen species(ROS)and promote ferroptosis in cells.this paper reviewed the non-coding RNAs involved in the regulation of ferroptosis in recent years,including small molecule RNA(microRNA),long non-coding RNA(lncRNA),and circular RNA(circRNA).Studies have found that non-coding RNA can also regulate glutathione(GSH)synthesis,lipid ROS and GPX4 activity,which plays a pivotal role in the process of ferroptosis in various diseases,especially in tumor diseases.
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维普
