生物
癌变
组蛋白
癌症研究
表观遗传学
组蛋白甲基转移酶
组蛋白甲基化
组蛋白H2A
癌症
基因表达
遗传学
基因
DNA甲基化
作者
Jie Yu,Peiwei Chai,Meng Xie,Shengfang Ge,Jing Ruan,Xianqun Fan
出处
期刊:Genome Biology
[Springer Nature]
日期:2021-03-16
卷期号:22 (1)
被引量:260
标识
DOI:10.1186/s13059-021-02308-z
摘要
Abstract Background Histone lactylation, a metabolic stress-related histone modification, plays an important role in the regulation of gene expression during M1 macrophage polarization. However, the role of histone lactylation in tumorigenesis remains unclear. Results Here, we show histone lactylation is elevated in tumors and is associated with poor prognosis of ocular melanoma. Target correction of aberrant histone lactylation triggers therapeutic efficacy both in vitro and in vivo. Mechanistically, histone lactylation contributes to tumorigenesis by facilitating YTHDF2 expression. Moreover, YTHDF2 recognizes the m6A modified PER1 and TP53 mRNAs and promotes their degradation, which accelerates tumorigenesis of ocular melanoma. Conclusion We reveal the oncogenic role of histone lactylation, thereby providing novel therapeutic targets for ocular melanoma therapy. We also bridge histone modifications with RNA modifications, which provides novel understanding of epigenetic regulation in tumorigenesis.
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