ACSL4基因表达的调控机制  

The regulatory mechanism of ACSL4 gene expression

作　　者：沈子月 谭理 SHEN Ziyue;TAN Li(Medical Research and Innovation Center,Fudan University Affiliated Pudong Hospital,Shanghai 201339,China;Laboratory of Epigenetics,Institute of Biomedical Sciences,Fudan University,Shanghai 200032,China;School of Basic Medical Sciences,Fudan University,Shanghai 200032,China)

机构地区：[1]复旦大学附属浦东医院医学科研与创新中心,上海201339 [2]复旦大学生物医学研究院上海市表观遗传学重点实验室,上海200032 [3]复旦大学基础医学院,上海200032

出　　处：《生命的化学》2024年第6期951-964,共14页Chemistry of Life

基　　金：国家自然科学基金项目(82073113,82273136)。

摘　　要：长链酰基辅酶A合酶4(long-chain acyl-coenzyme A synthase 4,ACSL4)是ACSLs家族的成员。ACSL4是催化长链脂肪酸活化的关键酶,在脂质代谢通路中发挥重要作用。此外,ACSL4推动细胞内脂质过氧化的发生,是铁死亡敏感性的关键决定因素。ACSL4的异常表达与各种生物学反应密切相关。同时由于对肿瘤细胞的铁死亡敏感性有重要影响,ACSL4有望成为可用的肿瘤生物标志物和治疗靶点。阐明ACSL4的表达调控分子机制对于进一步研究脂质代谢通路、铁死亡调控通路以及发现新的肿瘤靶向治疗策略具有重大意义。本文主要从表观遗传水平、转录水平、转录后水平(miRNA和mRNA修饰)、翻译后水平等方面综述了近年来ACSL4基因表达调控的最新进展。Long-chain acyl-coenzyme A synthase 4(ACSL4)is a member of the ACSLs family.ACSL4 is a key enzyme activating long-chain fatty acids and plays an important role in the lipid metabolism pathway.In addition,researches have proved that,as a key determinant of ferroptosis sensitivity,ACSL4 drives the process of lipid peroxidation intracellularly.Aberrant expression of ACSL4 is closely associated with various biological responses,and is expected to be a usable tumor biomarker and therapeutic target due to its important influence on the ferroptosis sensitivity of tumor cells.Elucidating the molecular mechanism of ACSL4expression is of great significance for further investigation of lipid metabolism,ferroptosis regulatory pathways and the discovery of novel tumor-targeted therapeutic strategies.Here,we summarize the recent progress in ACSL4 gene expression regulation mechanism including epigenetic,transcriptional,posttranscriptional(miRNA and mRNA modification)and post-translational regulation.

关 键 词：长链酰基辅酶A合酶4 铁死亡 分子调控 

分 类 号：Q75[生物学—分子生物学]